Pyrimidine Derivatives And Their Use As Herbicides

Abstract

The present invention relates to substituted pyrimidine derivatives, as well as N-oxides thereof and agriculturally acceptable salts thereof, and their use to control undesired plant growth, in particular in crops of useful plants. The invention extends to herbicidal compositions comprising such compounds, N-oxides and/or salts as well as mixtures of the same with one or more further active ingredient (such as, for example, an herbicide, fungicide, insecticide and/or plant growth regulator) and/or a safener. The invention further relates to intermediates useful in the preparation of such compounds, and to processes for their preparation.

Description

[0001] The present invention relates to substituted pyrimidine derivatives, as well as N-oxides thereof and agriculturally acceptable salts thereof, their use to control undesired plant growth, in particular in crops of useful plants, to processes for their preparation, and intermediates useful in such processes. The invention extends to herbicidal compositions comprising such compounds, N-oxides and/or salts as well as mixtures of the same with one or more further active ingredient (such as, for example, an herbicide, fungicide, insecticide and/or plant growth regulator) and/or a safener.

[0002] Substituted pyrimidine derivatives and their use as herbicides are disclosed in International Patent Publication No. WO 2005/063721. International Patent Publication No. WO 2007/082076 discloses a number of 2-(poly-substituted aryl)-6-amino-5-halo-4-pyrimidine carboxylic acids and their use as herbicides, whilst International Patent Publication No. WO 2007/092184 discloses certain substituted pyrimidine and pyridine carboxylic acid derivatives as compounds capable of improving the harvestability of crops. Further picolinic and pyrimidine acid derivatives are disclosed in WO2009/046090 and WO2009/029735.

[0003] In part, due to the evolution of herbicide-resistant weed populations, and herbicide-resistant crops becoming volunteer weeds, there is a continuing need to control such undesired plant growth in particular in crops of useful plants. Other factors, for example, the demand for cheaper, more effective herbicides, and for herbicides with an improved environmental profile (e.g. safer, less toxic etc.) also drive the need to identify novel herbicidal compounds.

[0004] The present invention seeks to address this need, and is based on the finding that substituted pyrimidine derivatives, in particular where the 5 position of the pyrimidine ring is substituted with an optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, or optionally substituted alkynyl group, are particularly effective herbicidal compounds.

[0005] Thus in a first aspect of the invention there is provided a compound of formula (I)

##STR00001##

[0006] or salt or N-oxide thereof,

[0007] wherein: [0008] A is halogen, optionally substituted alkylthio, optionally substituted alkyl, optionally substituted alkenyl or an optionally substituted 3-8 membered carbocyclic ring; [0009] X is azido, halogen, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkylsulphinyl, optionally substituted alkylsulphonyl or NR.sup.5R.sup.6; [0010] R.sup.5 is hydrogen, C.sub.2-4 alkenyl, SO.sub.2R.sup.ss, C(O)R.sup.uu or optionally substituted C.sub.1-4 alkyl; [0011] R.sup.6 is hydrogen, C.sub.2-4 alkenyl or optionally substituted C.sub.1-4 alkyl; [0012] each R.sup.ss is independently C.sub.1-4 alkyl or phenyl optionally substituted by 1-3 groups R.sup.zz; [0013] each R.sup.uu is independently C.sub.1-4 alkyl, phenyl optionally substituted by 1-3 groups R.sup.zz, C.sub.1-4 alkoxy, or NR.sup.acR.sup.ad; [0014] each R.sup.zz is independently halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, or C.sub.1-4 alkylsulphonyl; [0015] R.sup.ac and R.sup.ad are each independently hydrogen or C.sub.1-4 alkyl; [0016] or R.sup.5 and R.sup.6 together form a group .dbd.C(R.sup.i)OR.sup.j, .dbd.C(R.sup.k)SR.sup.l, .dbd.C(R.sup.m)NR.sup.nR.sup.o wherein [0017] R.sup.i is hydrogen, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, phenyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, or NR.sup.acR.sup.ad wherein R.sup.ac and R.sup.ad are as defined above, [0018] R.sup.j and R.sup.l are each independently C.sub.1-4 alkyl, [0019] R.sup.k is hydrogen, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, phenyl, C.sub.1-4 alkylthio, or NR.sup.acR.sup.ad wherein R.sup.ac and R.sup.ad are as defined above, [0020] R.sup.m is hydrogen, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, phenyl, or NR.sup.acR.sup.ad wherein R.sup.ac and R.sup.ad are as defined above, and [0021] R.sup.n and R.sup.o are each independently hydrogen or C.sub.1-4 alkyl; [0022] Y is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, or optionally substituted alkynyl; [0023] and, [0024] Z is O.sub.m--(CHR.sup.w).sub.n--C(O)R.sup.cb, wherein [0025] m is an integer of 0 or 1, [0026] n is an integer of 0 or 1 and n.gtoreq.m, [0027] R.sup.w is hydrogen or C.sub.1-4 alkyl [0028] R.sup.cb is hydroxy, optionally substituted alkylthio, NH.sub.2, or OR.sup.co, [0029] R.sup.co is C.sub.1-20 alkyl optionally substituted by 1-3 groups R.sup.cq, or C.sub.1-20 haloalkyl optionally substituted by 1-3 groups R.sup.cq; [0030] each R.sup.cq is independently C.sub.1-6 alkoxy, phenyl optionally substituted by 1-3 groups R.sup.cr, or heteroaryl optionally substituted by 1-2 groups R.sup.cs; [0031] each R.sup.cr and each R.sup.cs are independently halogen, cyano, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.2-6 alkoxyalkyl, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, C.sub.1-4 alkylsulphonyl, or C.sub.1-4 alkoxycarbonyl; [0032] provided that: [0033] i) when Y is C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.2-4 alkoxyalkyl, C.sub.2-4 alkylthioalkyl, C.sub.2-4 alkenyl, C.sub.2-4 haloalkenyl, C.sub.2-4 alkoxyalkenyl, C.sub.2-4 thioalkylalkenyl, C.sub.2-4 alkynyl, C.sub.2-4 haloalkynyl, C.sub.2-4 alkylcarbonyl or C.sub.2-4 haloalkylcarbonyl; [0034] X is NR.sup.5R.sup.6; [0035] R.sup.5 is H, C.sub.1-4 alkyl, C.sub.3-4 alkenyl, C.sub.1-4 alkylsulfonyl or C.sub.1-4 acyl; [0036] R.sup.6 is H, C.sub.1-4 alkyl or C.sub.3-4 alkenyl; [0037] A is C1-C6 alkyl, cyclopropyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl or a group of the formula

[0037] ##STR00002## [0038] W.sub.1 represents H or halogen; [0039] X.sub.1 represents H, halogen, nitro, cyano, formyl, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, C.sub.2-4 alkoxyalkyl, C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkylthio, C.sub.1-6 alkylsulfinyl, C.sub.1-6 alkylsulfonyl, C.sub.2-4 alkenyloxy, C.sub.2-4 alkynyloxy, C.sub.2-4 alkenylthio, C.sub.2-4 alkynylthio, C.sub.1-6 haloalkyl, C.sub.2-6 halo-alkenyl, C.sub.2-6 haloalkynyl, C.sub.1-6 haloalkoxy, C.sub.2-4 haloalkoxyalkyl, C.sub.2-6 haloalkylcarbonyl, C.sub.1-6 haloalkylthio, C.sub.1-6 haloalkylsulfinyl, C.sub.1-6 halo-.alkylsulfonyl, C.sub.3-6 trialkylsilyl, C.sub.2-4 haloalkenyloxy, C.sub.2-4 haloalkynyloxy, C.sub.2-4 haloalkenylthio, C.sub.2-4 haloalkynylthio, --C(O)OR.sup.7', --C(O)NR.sup.6'R.sup.7', --CR.sup.6'NOR.sup.7', --NR.sup.6'R.sup.7', --NR.sup.6'OR.sup.7', --NR.sup.6'SO2R.sup.7', --NR.sup.6'C(O)R.sup.7', --NR.sup.6'(O)OR.sup.7', --NR.sup.6'C(O)NR.sup.6'R.sup.7' or --NCR.sup.6'NR.sup.6'R.sup.7'; [0040] R.sup.6' represents H, C.sub.1-4 alkyl or C.sub.1-4 haloalkyl; [0041] R.sup.7' represents C.sub.1-4 alkyl or C.sub.1-4 haloalkyl; [0042] Y.sub.1 represents H, halogen, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.1-6 alkoxy, C.sub.1-6 haloalkoxy, C.sub.2-6 alkenyl or C.sub.2-6 haloalkenyl, or, X.sub.1 and Y.sub.1 taken together, represents --O(CH.sub.2).sub.nnCH.sub.2--, or --O(CH.sub.2).sub.nnO-- wherein nn=1 or 2; and [0043] Z.sub.1 represents H or halogen, then Z is other than CO.sub.2H, CO.sub.2Me, CO.sub.2Et, CO.sub.2.sup.nBu or CO.sub.2.sup.-NHEt.sub.3.sup.+. In a second aspect of the invention there is provided a herbicidal composition comprising a compound as defined above and at least one agriculturally acceptable formulation adjuvant or diluent.

[0044] In a second aspect of the invention there is provided a compound as defined above, or a herbicidal composition as defined above in admixture with at least one active ingredient selected from the group consisting of: an insecticide, an acaricide, a nematocide, a molluscicide, an herbicide, a fungicide, and a plant growth regulator.

[0045] In a third aspect of the invention there is provided a use of a compound according to the invention as a herbicide.

[0046] In a fourth aspect of the invention, there is provided a method of controlling weeds in crops of useful plants which comprises applying to said weeds or to the locus of said weeds, or to said crop of useful plants, a compound, composition or a mixture according to the invention.

[0047] In a fifth aspect of the invention, there is provided a compound of formula (II)

##STR00003##

wherein R.sup.7 is methyl, Br, or Cl;

R.sup.8 is H, F, Cl, OR.sup.10, or N(R.sup.10).sub.2;

R.sup.9 is H, F, or Cl; and

[0048] each R.sup.10 is independently H or C.sub.1-4alkyl, provided that (i) R.sup.8 and R.sup.9 are not both hydrogen, (ii) when R.sup.7 is methyl and R.sup.9 is hydrogen, then R.sup.8 is not F, Cl, or NH.sub.2, (iii) when R.sup.7 is Cl and R.sup.8 is hydrogen, R.sup.9 is not Cl, (iv) when R.sup.7 is Cl and R.sup.8 is Cl, R.sup.9 is not hydrogen, and (v) when R.sup.7 is Br and R.sup.9 is hydrogen, R.sup.8 is not F.

[0049] In a sixth aspect of the invention, there is provided a process for the preparation of a compound of formula (T)

##STR00004##

[0050] or salt or N-oxide thereof,

[0051] wherein: [0052] A is halogen, optionally substituted alkylthio, optionally substituted alkyl, optionally substituted alkenyl or an optionally substituted 3-8 membered carbocyclic ring; [0053] Y' is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, or optionally substituted alkynyl; [0054] and, [0055] Z' is hydroxyl or (CHR.sup.w).sub.n--C(O)R.sup.cb, wherein [0056] n is an integer of 0 or 1, [0057] R.sup.w is hydrogen or C.sub.1-4 alkyl [0058] R.sup.cb is hydroxy, optionally substituted alkylthio, optionally substituted alkyl, NH.sub.2, or OR.sup.co, [0059] R.sup.co is C.sub.1-20 alkyl optionally substituted by 1-3 groups R.sup.cq, or C.sub.1-20 haloalkyl optionally substituted by 1-3 groups R.sup.cq; [0060] each R.sup.cq is independently C1-6 alkoxy, phenyl optionally substituted by 1-3 groups R.sup.cr, or heteroaryl optionally substituted by 1-2 groups R.sup.cs; each R.sup.cr and each R.sup.cs are independently halogen, cyano, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.2-6 alkoxyalkyl, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, C.sub.1-4 alkylsulphonyl, or C.sub.1-4 alkoxycarbonyl comprising reacting an amidine of formula (N)

##STR00005##

[0060] wherein A is as defined above, or a salt form thereof, with a keto ester of the formula (U)

##STR00006##

or a salt form thereof, wherein Y' and Z' are as defined above, or Z' is OR, and R is selected from hydrogen or alkyl.

[0061] In an seventh aspect, there is provided a compound of formula (I)

##STR00007##

[0062] or salt or N-oxide thereof,

[0063] wherein: [0064] A is halogen, optionally substituted alkylthio, optionally substituted alkyl, optionally substituted alkenyl or an optionally substituted 3-8 membered carbocyclic ring; [0065] X is azido, halogen, optionally substituted alkoxy, or NR.sup.5R.sup.6; [0066] R.sup.5 is hydrogen, optionally substituted C.sub.1-4 alkyl provided said substitution does not comprise a ring system or a hydroxyl group, C.sub.2-4 alkenyl, SO.sub.2R.sup.ss, or C(O)R.sup.uu; [0067] R.sup.6 is hydrogen, optionally substituted C.sub.1-4 alkyl provided said substitution does not comprise a ring system or a hydroxyl group, C.sub.2-4 alkenyl; [0068] each R.sup.ss is independently C.sub.1-4 alkyl or phenyl optionally substituted by 1-3 groups R.sup.zz; [0069] each R.sup.uu is independently C.sub.1-4 alkyl, phenyl optionally substituted by 1-3 groups R.sup.zz, C.sub.1-4 alkoxy, or NR.sup.acR.sup.ad; [0070] each R.sup.zz is independently halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, or C.sub.1-4 alkylsulphonyl; [0071] R.sup.ac and R.sup.ad are each independently hydrogen or C.sub.1-4 alkyl; [0072] or R.sup.5 and R.sup.6 together form a group .dbd.C(R.sup.i)OR.sup.j, .dbd.C(R.sup.k)SR.sup.l, .dbd.C(R.sup.m)NR.sup.nR.sup.o wherein [0073] R.sup.i is hydrogen, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, phenyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, or NR.sup.acR.sup.ad wherein R.sup.ac and R.sup.ad are as defined above, [0074] R.sup.j and R.sup.l are each independently C.sub.1-4 alkyl, [0075] R.sup.k is hydrogen, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, phenyl, C.sub.1-4 alkylthio, or NR.sup.acR.sup.ad wherein R.sup.ac and R.sup.ad are as defined above, [0076] R.sup.m is hydrogen, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, phenyl, or NR.sup.acR.sup.ad wherein R.sup.ac and R.sup.ad are as defined above, and [0077] R.sup.n and R.sup.o are each independently hydrogen or C.sub.1-4 alkyl; [0078] Y is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, or optionally substituted alkynyl; [0079] and, [0080] Z is O.sub.m--(CHR.sup.w).sub.n--C(O)R.sup.cb, wherein [0081] m is an integer of 0 or 1, [0082] n is an integer of 0 or 1 and n.gtoreq.m, [0083] R.sup.w is hydrogen or C.sub.1-4 alkyl [0084] R.sup.cb is hydroxy, optionally substituted alkylthio, optionally substituted alkyl, NH.sub.2, or OR.sup.co, [0085] R.sup.co is C.sub.1-20 alkyl optionally substituted by 1-3 groups R.sup.cq, or C.sub.1-20 haloalkyl optionally substituted by 1-3 groups R.sup.cq; [0086] each R.sup.cq is independently phenyl optionally substituted by 1-3 groups R.sup.cr, or heteroaryl optionally substituted by 1-2 groups R.sup.cs; each R.sup.cr and each R.sup.cs are independently halogen, cyano, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.2-6 alkoxyalkyl, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, C.sub.1-4 alkylsulphonyl, or C.sub.1-4 alkoxycarbonyl.

[0087] For the avoidance of doubt, the term "compound" as used herein includes all salts and N-oxides of said compound.

[0088] The compounds of formula (I) may exist in different geometric or optical isomers or different tautomeric forms. One or more centres of chirality may be present, in which case compounds of the formula (I) may be present as pure enantiomers, mixtures of enantiomers, pure diastereomers or mixtures of diastereomers. There may be double bonds present in the molecule, such as C.dbd.C or C.dbd.N bonds, in which case compounds of formula (I) may exist as single isomers or mixtures of isomers. Centres of tautomerisation may be present. This invention covers all such isomers and tautomers and mixtures thereof in all proportions as well as isotopic forms such as deuterated compounds.

[0089] Suitable acid addition salts include those with an inorganic acid such as hydrochloric, hydrobromic, sulfuric, nitric and phosphoric acids, or an organic carboxylic acid such as oxalic, tartaric, lactic, butyric, toluic, hexanoic and phthalic acids, or sulphonic acids such as methane, benzene and toluene sulphonic acids. Other examples of organic carboxylic acids include haloacids such as trifluoroacetic acid.

[0090] Suitable salts also include those formed by strong bases (e.g. metal hydroxides--in particular sodium, potassium or lithium--or quaternary ammonium hydroxide) as well as those formed with amines.

[0091] N-oxides are oxidised forms of tertiary amines or oxidised forms of nitrogen containing heteroaromatic compounds. They are described in many books for example in "Heterocyclic N-oxides" by Angelo Albini and Silvio Pietra, CRC Press, Boca Raton, Fla., 1991.

[0092] Each alkyl moiety either alone or as part of a larger group (such as alkoxy, alkoxyalkyl, alkylcarbonyl, alkoxycarbony, alkylaminocarbonyl, alkylsulphonyl, alkylthio, hakoalkylthio, haloalkyl, haloalkoxy, trialklylsilyl, etc.) is a straight or branched chain and is, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, iso-propyl, sec-butyl, iso-butyl, tert-butyl or neo-pentyl. As defined herein alkyl groups may be C.sub.1 to C.sub.20 alkyl groups, but are typically C.sub.1-10, preferably C.sub.1-C.sub.6, more preferably C.sub.1-C.sub.4, even more preferably C.sub.1-3, and most preferably C.sub.1-C.sub.2 alkyl groups.

[0093] Ring or chain forming alkylene, alkenylene and alkynylene groups can optionally be further substituted by one or more halogen, C.sub.1-3 alkyl and/or C.sub.1-3 alkoxy groups.

[0094] When present, the optional substituents on an alkyl moiety (alone or as part of a larger group) include one or more of halogen, nitro, cyano, C.sub.3-7 cycloalkyl (itself optionally substituted with C.sub.1-6 alkyl or halogen), C.sub.5-7 cycloalkenyl (itself optionally substituted with C.sub.1-6 alkyl or halogen), hydroxy, C.sub.1-10 alkoxy, C.sub.1-10 alkoxy(C.sub.1-10)alkoxy, C.sub.1-6 alkoxycarbonyl(C.sub.1-10)alkoxy, C.sub.1-10 haloalkoxy, aryl(C.sub.1-4-alkoxy (where the aryl group is optionally substituted), C.sub.3-7 cycloalkyloxy (where the cycloalkyl group is optionally substituted with C.sub.1-6 alkyl or halogen), C.sub.2-10 alkenyloxy, C.sub.2-10 alkynyloxy, mercapto, C.sub.1-10 alkylthio, C.sub.1-10 haloalkylthio, aryl(C.sub.1-4alkylthio (where the aryl group is optionally substituted), C.sub.3-7 cycloalkylthio (where the cycloalkyl group is optionally substituted with C.sub.1-6 alkyl or halogen), arylthio (where the aryl group is optionally substituted), C.sub.1-6 alkylsulfonyl, C.sub.1-6 haloalkylsulfonyl, C.sub.1-6 alkylsulfinyl, C.sub.1-6 haloalkylsulfinyl, arylsulfonyl (where the aryl group may be optionally substituted), tri(C.sub.1-4)alkylsilyl, aryl(C.sub.1-4)alkylthio(C.sub.1-4)alkyl, aryloxy(C.sub.1-4)alkyl, formyl, C.sub.1-10 alkylcarbonyl, HO.sub.2C, C.sub.1-10 alkoxycarbonyl, aminocarbonyl, C.sub.1-6 alkylaminocarbonyl, di(C.sub.1-6 alkyl)aminocarbonyl, N--(C.sub.1-3 alkyl)-N--(C.sub.1-3 alkoxy)aminocarbonyl, C.sub.1-6 alkylcarbonyloxy, arylcarbonyloxy (where the aryl group is optionally substituted), di(C.sub.1-6)alkylaminocarbonyloxy, oximes and oxime-ethers such as .dbd.NOalkyl, .dbd.NOhaloalkyl and .dbd.NOaryl (itself optionally substituted), aryl (itself optionally substituted), heteroaryl (itself optionally substituted), heterocyclyl (itself optionally substituted with C.sub.1-6 alkyl or halogen), aryloxy (where the aryl group is optionally substituted), heteroaryloxy, (where the heteroaryl group is optionally substituted), heterocyclyloxy (where the heterocyclyl group is optionally substituted with C.sub.1-6 alkyl or halogen), amino, C.sub.1-6 alkylamino, di(C.sub.1-6)alkylamino, C.sub.1-6 alkylcarbonylamino, N--(C.sub.1-6)alkylcarbonyl-N--(C.sub.1-6)alkylamino, C.sub.2-6 alkenylcarbonyl, C.sub.2-6 alkynylcarbonyl, C.sub.3-6 alkenyloxycarbonyl, C.sub.3-6 alkynyloxycarbonyl, aryloxycarbonyl (where the aryl group is optionally substituted) and arylcarbonyl (where the aryl group is optionally substituted).

[0095] Alkenyl and alkynyl moieties can be in the form of straight or branched chains, and the alkenyl moieties, where appropriate, can be of either the (E)- or (Z)-configuration. Preferably alkenyl moieties are C.sub.2-6 alkenyl groups, more preferably C.sub.2-4 alkenyl groups, and most preferably vinyl or allyl. Alkynyl moieties are preferably C.sub.2-6 alkynyl groups, more preferably C.sub.2-4 alkynyl groups and most prefereably ethynyl and propargyl. Alkenyl and alkynyl moieties can contain one or more double and/or triple bonds in any combination. It is understood, that allenyl and alkynylalkenyl are included in these terms.

[0096] When present, the optional substituents on alkenyl or alkynyl include those optional substituents given above for an alkyl moiety.

[0097] In the context of this specification acyl is optionally substituted C.sub.1-6 alkylcarbonyl (for example acetyl), optionally substituted C.sub.2-6 alkenylcarbonyl, optionally substituted C.sub.3-6 cycloalkylcarbonyl (for example cyclopropylcarbonyl), optionally substituted C.sub.2-6 alkynylcarbonyl, optionally substituted arylcarbonyl (for example benzoyl) or optionally substituted heteroarylcarbonyl.

[0098] Halogen is fluorine, chlorine, bromine or iodine.

[0099] Haloalkyl groups are alkyl groups which are substituted with one or more of the same or different halogen atoms and are, for example, CF.sub.3, CF.sub.2Cl, CF.sub.2H, CCl.sub.2H, FCH.sub.2, ClCH.sub.2, BrCH.sub.2, CH.sub.3CHF, (CH.sub.3).sub.2CF, CF.sub.3CH.sub.2 or CHF.sub.2CH.sub.2.

[0100] In the context of the present specification ring systems may be saturated, unsaturated, or aromatic, and may also be fused, spiro or bridging ring systems. The terms "aryl", "aromatic ring" and "aromatic ring system" as used herein refer to ring systems which may be mono-, bi- or tricyclic. Examples of such rings include phenyl, naphthalenyl, anthracenyl, indenyl or phenanthrenyl. A preferred aryl group is phenyl. In addition, the terms "heteroaryl", "heteroaromatic ring" or "heteroaromatic ring system" refer to an aromatic ring system containing at least one heteroatom and consisting either of a single ring or of two or more fused rings. Preferably, single rings will contain up to three and bicyclic systems up to four heteroatoms which will preferably be chosen from nitrogen, oxygen and sulphur. Examples of such groups include furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, benzofuryl, benzisofuryl, benzothienyl, benzisothienyl, indolyl, isoindolyl, indazolyl, benzothiazolyl, benzisothiazolyl, benzoxazolyl, benzisoxazolyl, benzimidazolyl, 2,1,3-benzoxadiazole, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, benzotriazinyl, purinyl, pteridinyl and indolizinyl. Preferred examples of heteroaromatic radicals include pyridyl, pyrimidyl, triazinyl, thienyl, furyl, oxazolyl, isoxazolyl and thiazolyl.

[0101] The terms heterocycle and heterocyclyl refer to a non-aromatic preferably monocyclic or bicyclic ring systems containing up to 10 atoms including one or more (preferably one or two) heteroatoms selected from O, S and N. Examples of such rings include 1,3-dioxolane, oxetane, tetrahydrofuran, morpholine, thiomorpholine and piperazine.

[0102] In the case of heteroaromatic or heterocyclic rings containing S as a heteroatom, the S atom may also be in the form of a mono- or di-oxide.

[0103] When present, the optional substituents on heterocyclyl include C.sub.1-6 alkyl and C.sub.1-6 haloalkyl, an oxo-group (allowing one of the carbon atoms in the ring to be in the form of a keto group), as well as those optional substituents given above for an alkyl moiety.

[0104] Cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. Cycloalkylalkyl is preferentially cyclopropylmethyl. Cycloalkenyl includes cyclopentenyl and cyclohexenyl.

[0105] When present, the optional substituents on cycloalkyl or cycloalkenyl include C.sub.1-3 alkyl as well as those optional substituents given above for an alkyl moiety.

[0106] Carbocyclic rings include aryl, cycloalkyl and cycloalkenyl groups.

[0107] When present, the optional substituents on aryl or heteroaryl are selected independently, from halogen, nitro, cyano, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.1-6 alkoxy-(C.sub.1-6)alkyl, C.sub.2-6 alkenyl, C.sub.2-6 haloalkenyl, C.sub.2-6 alkynyl, C.sub.3-7 cycloalkyl (itself optionally substituted with C.sub.1-6 alkyl or halogen), C.sub.5-7 cycloalkenyl (itself optionally substituted with C.sub.1-6 alkyl or halogen), hydroxy, C.sub.1-10 alkoxy, C.sub.1-10 alkoxy(C.sub.1-10)alkoxy, tri(C.sub.1-4)alkyl-silyl(C.sub.1-6)alkoxy, C.sub.1-6 alkoxycarbonyl(C.sub.1-10)alkoxy, C.sub.1-10 haloalkoxy, aryl(C.sub.1-4)alkoxy (where the aryl group is optionally substituted with halogen or C.sub.1-6 alkyl), C.sub.3-7 cycloalkyloxy (where the cycloalkyl group is optionally substituted with C.sub.1-6 alkyl or halogen), C.sub.2-10 alkenyloxy, C.sub.2-10 alkynyloxy, mercapto, C.sub.1-10 alkylthio, C.sub.1-10 haloalkylthio, aryl(C.sub.1-4)alkylthio, C.sub.3-7 cycloalkylthio (where the cycloalkyl group is optionally substituted with C.sub.1-6 alkyl or halogen), tri(C.sub.1-4-alkylsilyl(C.sub.1-6)alkylthio, arylthio, C.sub.1-6 alkylsulfonyl, C.sub.1-6 haloalkylsulfonyl, C.sub.1-6 alkylsulfinyl, C.sub.1-6 haloalkylsulfinyl, arylsulfonyl, tri(C.sub.1-4)alkylsilyl, aryldi(C.sub.1-4-alkylsilyl, (C.sub.1-4)alkyldiarylsilyl, triarylsilyl, C.sub.1-10 alkylcarbonyl, HO.sub.2C, C.sub.1-10 alkoxycarbonyl, aminocarbonyl, C.sub.1-6 alkylaminocarbonyl, di(C.sub.1-6 alkyl)-aminocarbonyl, N--(C.sub.1-3 alkyl)-N--(C.sub.1-3 alkoxy)aminocarbonyl, C.sub.1-6 alkylcarbonyloxy, arylcarbonyloxy, di(C.sub.1-6)alkylamino-carbonyloxy, aryl (itself optionally substituted with C.sub.1-6 alkyl or halogen), heteroaryl (itself optionally substituted with C.sub.1-6 alkyl or halogen), heterocyclyl (itself optionally substituted with C.sub.1-6 alkyl or halogen), aryloxy (where the aryl group is optionally substituted with C.sub.1-6 alkyl or halogen), heteroaryloxy (where the heteroaryl group is optionally substituted with C.sub.1-6 alkyl or halogen), heterocyclyloxy (where the heterocyclyl group is optionally substituted with C.sub.1-6 alkyl or halogen), amino, C.sub.1-6 alkylamino, di(C.sub.1-6)alkylamino, C.sub.1-6 alkylcarbonylamino, N--(C.sub.1-6)alkylcarbonyl-N--(C.sub.1-6)alkylamino, arylcarbonyl, (where the aryl group is itself optionally substituted with halogen or C.sub.1-6 alkyl) or two adjacent positions on an aryl or heteroaryl system may be cyclised to form a 5, 6 or 7 membered carbocyclic or heterocyclic ring, itself optionally substituted with halogen or C.sub.1-6 alkyl. Further substituents for aryl or heteroaryl include arylcarbonylamino (where the aryl group is substituted by C.sub.1-6 alkyl or halogen), C.sub.1-6alkoxycarbonylamino, C.sub.1-6alkoxycarbonyl-N--(C.sub.1-6)alkylamino, aryloxycarbonylamino (where the aryl group is substituted by C.sub.1-6 alkyl or halogen), aryloxycarbonyl-N--(C.sub.1-6)alkylamino (where the aryl group is substituted by C.sub.1-6 alkyl or halogen), arylsulphonylamino (where the aryl group is substituted by C.sub.1-6 alkyl or halogen), arylsulphonyl-N--(C.sub.1-6)alkylamino (where the aryl group is substituted by C.sub.1-6 alkyl or halogen), aryl-N--(C.sub.1-6)alkylamino (where the aryl group is substituted by C.sub.1-6 alkyl or halogen), arylamino (where the aryl group is substituted by C.sub.1-6 alkyl or halogen), heteroarylamino (where the heteroaryl group is substituted by C.sub.1-6 alkyl or halogen), heterocyclylamino (where the heterocyclyl group is substituted by C.sub.1-6 alkyl or halogen), aminocarbonylamino, C.sub.1-6 alkylaminocarbonylamino, di(C.sub.1-6)alkylaminocarbonylamino, arylaminocarbonylamino where the aryl group is substituted by C.sub.1-6 alkyl or halogen), aryl-N--(C.sub.1-6)alkylaminocarbonylamino (where the aryl group is substituted by C.sub.1-6 alkyl or halogen), C.sub.1-6 alkylaminocarbonyl-N--(C.sub.1-6)alkylamino, di(C.sub.1-6)alkylaminocarbonyl-N--(C.sub.1-6)alkylamino, arylaminocarbonyl-N--(C.sub.1-6)alkylamino (where the aryl group is substituted by C.sub.1-6 alkyl or halogen) and aryl-N--(C.sub.1-6)alkylaminocarbonyl-N--(C.sub.1-6)alkylamino (where the aryl group is substituted by C.sub.1-6 alkyl or halogen).

[0108] For substituted phenyl moieties, heterocyclyl and heteroaryl groups it is preferred that one or more substituents are independently selected from halogen, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.1-6 alkoxy(C.sub.1-6)alkyl, C.sub.1-6 alkoxy, C.sub.1-6 haloalkoxy, C.sub.1-6 alkylthio, C.sub.1-6 haloalkylthio, C.sub.1-6 alkylsulfinyl, C.sub.1-6 haloalkylsulfinyl, C.sub.1-6 alkylsulfonyl, C.sub.1-6 haloalkylsulfonyl, C.sub.2-6 alkenyl, C.sub.2-6 haloalkenyl, C.sub.2-6 alkynyl, C.sub.3-7 cycloalkyl, nitro, cyano, CO.sub.2H, C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkoxycarbonyl, aryl, heteroaryl, C.sub.1-6 alkylamino, di(C.sub.1-6 alkyl)amino, C.sub.1-6 alkylaminocarbonyl, or di(C.sub.1-6 alkyl)aminocarbonyl.

[0109] Haloalkenyl groups are alkenyl groups which are substituted with one or more of the same or different halogen atoms.

[0110] It is to be understood that dialkylamino substituents include those where the dialkyl groups together with the N atom to which they are attached form a five, six or seven-membered heterocyclic ring which may contain one or two further heteroatoms selected from O, N or S and which is optionally substituted by one or two independently selected (C.sub.1-6)alkyl groups. When heterocyclic rings are formed by joining two groups on an N atom, the resulting rings are suitably pyrrolidine, piperidine, thiomorpholine and morpholine each of which may be substituted by one or two independently selected (C.sub.1-6) alkyl groups.

[0111] In preferred embodiments of the invention, the preferred groups for A, X, Y, and Z, in any combination thereof, are as set out below.

[0112] According to the invention A is selected from halogen, optionally substituted alkylthio, optionally substituted alkyl, optionally substituted alkenyl and an optionally substituted 3-8 membered carbocyclic ring. Preferably, A is optionally substituted alkylthio.

[0113] In preferred embodiments A is selected from: halogen, C.sub.1-4 alkylthio, phenyl optionally substituted by 1-3 groups R.sup.1, and C.sub.3-6 cycloalkyl optionally substituted by 1-4 groups R.sup.2.

[0114] More preferably A is Cl, phenyl optionally substituted by 1-3 groups R.sup.1, or cyclopropyl optionally substituted by 1-2 groups R.sup.2.

[0115] Most preferably A is selected from the group consisting of: Cl, methylthio, isopropyl, cyclopropyl, 2-methylcyclopropyl, 4-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 4-trifluoromethoxyphenyl, 2,4-dimethoxyphenyl, 2,4-dichlorophenyl, 2-chloro-4-methylphenyl, 2-chloro-4-trifluoromethylphenyl, 2-fluoro-4-methylphenyl, 2-fluoro-3-methoxyphenyl, 2-fluoro-4-methoxyphenyl, 2,4-bis(trifluoromethyl)phenyl, 3,4-dimethylphenyl, 3,4-dimethoxyphenyl, 3-chloro-4-methylphenyl, 3-chloro-4-methoxyphenyl, 3,4-dichlorophenyl, 3-chloro-4-fluorophenyl, 3-chloro-4-trifluoromethylphenyl, 3-fluoro-4-methylphenyl, 3-fluoro-4-methoxyphenyl, 4-methyl-3-nitrophenyl, 4-methoxy-2-methylphenyl, 4-chloro-2-methylphenyl, 4-chloro-3-methylphenyl, 4-chloro-2-methoxyphenyl, 4-chloro-3-methoxyphenyl, 4-chloro-3-nitrophenyl, 4-chloro-3-cyanophenyl, 4-chloro-2-fluorophenyl, 4-chloro-3-fluorophenyl, 4-chloro-2-trifluoromethylphenyl, 4-chloro-3-trifluoromethylphenyl, 4-fluoro-3-methylphenyl, 4-fluoro-3-methoxyphenyl, 4-fluoro-3-trifluoromethylphenyl, 2,4,5-trimethylphenyl, 2,3,4-trimethoxyphenyl, 2,3,4-trichlorophenyl, 2,4,5-trichlorophenyl, 2,4,6-trichlorophenyl, 2,3,4-trifluorophenyl, 2,4-dichloro-3-fluorophenyl, 3,4-dichloro-2-fluorophenyl, 4-chloro-2,3-difluorophenyl, 4-chloro-2,6-difluorophenyl, 4-chloro-3,5-difluorophenyl, 2,4-dichloro-6-fluorophenyl, 4-chloro-2-fluoro-3-methoxyphenyl, 4-chloro-2-fluoro-3-trifluoromethylphenyl, 4-chloro-3-dimethylamino-2-fluorophenyl, and 2-fluoro-3-methoxy-4-methylphenyl.

[0116] Each R.sup.1 is independently halogen, cyano, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, C.sub.1-4 alkylthio, C.sub.1-4 haloalkylthio, amino, C.sub.1-4 alkylamino, di(C.sub.1-4)alkylamino, or two adjacent groups R.sup.1 together with the atoms to which they are joined form a 6-membered aromatic ring, said ring being optionally substituted by 1-2 groups selected from: halogen, cyano, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, C.sub.1-4 alkylthio, C.sub.1-4 haloalkylthio. Preferably each R.sup.1 is independently halogen, cyano, C.sub.1-2 alkyl, C.sub.1-2 haloalkyl, C.sub.1-2 alkoxy, C.sub.1-2 haloalkoxy, amino, C.sub.1-4 alkylamino, or di(C.sub.1-4)alkylamino.

[0117] Each R.sup.2 is independently halogen, cyano, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.3-6 cycloalkyl, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, C.sub.1-4 alkoxycarbonyl, or C.sub.1-4 alkylaminocarbonyl; or any two geminal R.sup.2 groups together form a group selected from oxo, .dbd.CR.sup.mmR.sup.nn, or .dbd.NOR.sup.oo; or two groups R.sup.2 together with the atoms to which they are joined form a 3-6-membered ring system, said ring system being optionally substituted by 1-2 groups selected from: halogen, cyano, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy, or C.sub.1-4 haloalkoxy. Preferably R.sup.2 is halogen, cyano, C.sub.1-2 alkyl, C.sub.1-2 haloalkyl, C.sub.1-2 alkoxy, C.sub.1-2 haloalkoxy or C.sub.2-4 alkoxycarbonyl. R.sup.mm and R.sup.nn are each independently hydrogen, halogen, cyano, nitro, C.sub.1-4 alkyl, or C.sub.1-4 alkoxycarbonyl. R.sup.oo is hydrogen, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl(C.sub.1-2)alkyl or C.sub.3-6 cycloalkyl.

[0118] According to the invention X is selected from: azido, halogen, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkylsulphinyl, optionally substituted alkylsulphonyl and NR.sup.5R.sup.6, where R.sup.5 and R.sup.6 are as defined hereinbefore.

[0119] In preferred embodiments X is selected from: azido, halogen, C.sub.1-3 alkoxy, C.sub.1-4 alkoxycarbonylC.sub.1-3alkoxy, and NR.sup.5R.sup.6. Most preferably X is N.sub.3, Cl, OCH.sub.3, OCH.sub.2CO.sub.2CH.sub.3, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, NH-isopropyl, NHCOCH.sub.3, NHC(O)OCH.sub.3, NHSO.sub.2CH.sub.3, NCH.sub.3COCH.sub.3, NCH.sub.3C(O)OCH.sub.3, or NCH.sub.3SO.sub.2CH.sub.3.

[0120] In alternative preferred embodiments, X is selected from: azido, halogen, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkylsulphinyl and optionally substituted alkylsulphonyl. More preferably, X is selected from: optionally substituted alkylthio, optionally substituted alkylsulphinyl and optionally substituted alkylsulphonyl.

[0121] Preferably R.sup.5 is hydrogen, C.sub.1-4 alkyl optionally substituted with 1 or 2 hydroxy or C.sub.1-4 alkoxy groups, C.sub.1-4 haloalkyl optionally substituted with 1 or 2 hydroxy or C.sub.1-4 alkoxy groups, C.sub.2-4 alkenyl, SO.sub.2R.sup.ss, or C(O)R.sup.uu, wherein R.sup.ss and R.sup.uu are as defined hereinbefore. In more preferred embodiments, R.sup.ss and R.sup.uu are each independently C.sub.1-3 alkyl.

[0122] Preferably R.sup.6 is hydrogen, C.sub.1-4 alkyl optionally substituted with 1 or 2 hydroxy or C.sub.1-4 alkoxy groups, C.sub.1-4 haloalkyl optionally substituted with 1 or 2 hydroxy or C.sub.1-4 alkoxy groups, or C.sub.2-4 alkenyl.

[0123] Alternatively, and preferably, R.sup.5 is hydrogen, C.sub.2-4 alkenyl, SO.sub.2R.sup.ss, C(O)R.sup.uu or optionally substituted C.sub.1-4 alkyl provided said substitution does not comprise a ring system or a hydroxyl group;

[0124] Alternatively, and preferably, R.sup.6 is hydrogen, C.sub.2-4 alkenyl or optionally substituted C.sub.1-4 alkyl provided said substitution does not comprise a ring system or a hydroxyl group;

[0125] In preferred embodiments of the present invention Y is C.sub.1-6 alkyl optionally substituted by 1-3 groups R.sup.ba, C.sub.1-6 haloalkyl optionally substituted by 1-3 groups R.sup.ba, C.sub.3-6 cycloalkyl optionally substituted by 1-3 groups R.sup.bc, C.sub.2-6alkenyl optionally substituted by 1-3 groups R.sup.bd, or C.sub.2-6 alkynyl optionally substituted by 1-3 groups R.sup.be.

[0126] In more preferred embodiments Y is C.sub.1-3 alkyl, C.sub.1-3 haloalkyl, C.sub.2-5alkoxyalkyl, cyclopropyl optionally substituted by 1 or 2 groups R.sup.bc, C.sub.2-4 alkenyl, C.sub.2-4 haloalkenyl, or C.sub.2-4 alkynyl optionally substituted by 1 or 2 groups R.sup.be.

[0127] More preferably still, Y is selected from the group consisting of: methyl, ethyl, isopropyl, n-propyl, prop-1-en-2-yl, prop-1-enyl, prop-2-enyl, but-1-enyl, pent-1-enyl, difluoromethyl, trifluoromethyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1-methylprop-1-enyl, 2-methylprop-1-enyl, 1,2-dimethylprop-1-enyl, 3-methylbut-1-ynyl, 3-methylbut-2-enyl, 3,3-dimethylbut-1-ynyl, acetyl, formyl, methoxymethyl, 2-methoxyethyl, hydroxyiminomethyl, methoxyiminomethyl, 1-(hydroxyimino)ethyl, 1-(methoxyimino)ethyl, cyclopropyl, 1-methylcyclopropyl, 2,2-dichlorocyclopropyl, vinyl, 2-cyclopropylvinyl, 1-ethoxyvinyl, 2,2-dichlorovinyl, ethynyl, prop-1-ynyl, 2-bromoethynyl, 2-chloroethynyl, and 2-trimethylsilylethynyl.

[0128] Each R.sup.ba is independently cyano, nitro, hydroxyl, C.sub.3-6 cycloalkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, C.sub.1-4 alkylcarbonyl or C.sub.1-4 alkoxycarbonyl, or two geminal R.sup.ba together form an oxo or oximino group.

[0129] Each R.sup.bc is independently halogen, cyano, C.sub.1-4alkoxy, or C.sub.1-4 alkoxycarbonyl. Preferably each R.sup.bc is independently halogen or C.sub.1-2 alkyl.

[0130] Each R.sup.bd is independently halogen, cyano, C.sub.3-6cycloalkyl, C.sub.1-4alkylcarbonyl, or C.sub.1-4 alkoxycarbonyl.

[0131] Each R.sup.be is independently halogen, cyano, hydroxyl, C.sub.1-4alkoxycarbonyl, or C.sub.3-12 trialkylsilyl. Preferably each R.sup.be is independently halogen or C.sub.3-9 trialkylsilyl.

[0132] In preferred embodiments of the invention Z is O.sub.m--(CH.sub.2).sub.n--C(O)R.sup.cb, wherein n is an integer of 0 or 1, m is an integer of 0 or 1, and both .sub.n and .sub.m have the same value, and wherein R.sup.cb is hydroxyl, C.sub.1-10 alkoxy, phenyl C.sub.1-2 alkoxy or NH.sub.2. More preferably still Z is selected from the group consisting of CO.sub.2H, CO.sub.2CH.sub.3, CO.sub.2CH.sub.2CH.sub.3, CO.sub.2-i-propyl, CO.sub.2-n-propyl, CO.sub.2CH.sub.2-i-propyl, CO.sub.2CH.sub.2-Phenyl, CONH.sub.2, OCH.sub.2CO.sub.2H, OCH.sub.2CO.sub.2CH.sub.3.

[0133] In alternative, preferred embodiments, Z is O.sub.m--(CHR.sup.w).sub.n--C(O)R.sup.cb, wherein [0134] m is an integer of 0 or 1, [0135] n is an integer of 0 or 1 and n.gtoreq.m, [0136] R.sup.w is hydrogen or C.sub.1-4 alkyl [0137] R.sup.cb is optionally substituted alkylthio, optionally substituted alkoxy or NH.sub.2.

[0138] The compounds described below are illustrative of novel compounds of the invention. Table 1 below provides 402 compounds designated compound numbers 1-1 to 1-402 respectively, of formula (I) wherein A is chloro, and wherein the values of X, Y and Z are as given in Table 1.

TABLE-US-00001 TABLE 1 Cmpd. No. X Y Z 1-1 NH.sub.2 methyl CO.sub.2H 1-2 NH.sub.2 ethyl CO.sub.2H 1-3 NH.sub.2 n-propyl CO.sub.2H 1-4 NH.sub.2 isopropyl CO.sub.2H 1-5 NH.sub.2 difluoromethyl CO.sub.2H 1-6 NH.sub.2 trifluoromethyl CO.sub.2H 1-7 NH.sub.2 hydroxymethyl CO.sub.2H 1-8 NH.sub.2 methoxymethyl CO.sub.2H 1-9 NH.sub.2 1-hydroxyethyl CO.sub.2H 1-10 NH.sub.2 2-hydroxyethyl CO.sub.2H 1-11 NH.sub.2 2-methoxyethyl CO.sub.2H 1-12 NH.sub.2 formyl CO.sub.2H 1-13 NH.sub.2 acetyl CO.sub.2H 1-14 NH.sub.2 hydroxyiminomethyl CO.sub.2H 1-15 NH.sub.2 methoxyiminomethyl CO.sub.2H 1-16 NH.sub.2 1-(hydroxyimino)ethyl CO.sub.2H 1-17 NH.sub.2 1-(methoxyimino)ethyl CO.sub.2H 1-18 NH.sub.2 cyclopropyl CO.sub.2H 1-19 NH.sub.2 1-methylcyclopropyl CO.sub.2H 1-20 NH.sub.2 2,2-dichlorocyclopropyl CO.sub.2H 1-21 NH.sub.2 vinyl CO.sub.2H 1-22 NH.sub.2 prop-1-enyl CO.sub.2H 1-23 NH.sub.2 prop-2-enyl CO.sub.2H 1-24 NH.sub.2 prop-1-en-2-yl CO.sub.2H 1-25 NH.sub.2 pent-1-enyl CO.sub.2H 1-26 NH.sub.2 2-cyclopropylvinyl CO.sub.2H 1-27 NH.sub.2 1-ethoxyvinyl CO.sub.2H 1-28 NH.sub.2 1-methylprop-1-enyl CO.sub.2H 1-29 NH.sub.2 2-methylprop-1-enyl CO.sub.2H 1-30 NH.sub.2 1,2-dimethylprop-1-enyl CO.sub.2H 1-31 NH.sub.2 2,2-dichlorovinyl CO.sub.2H 1-32 NH.sub.2 3-methylbut-2-enyl CO.sub.2H 1-33 NH.sub.2 ethynyl CO.sub.2H 1-34 NH.sub.2 prop-1-ynyl CO.sub.2H 1-35 NH.sub.2 but-1-ynyl CO.sub.2H 1-36 NH.sub.2 3-methylbut-1-ynyl CO.sub.2H 1-37 NH.sub.2 3,3-dimethylbut-1-ynyl CO.sub.2H 1-38 NH.sub.2 2-trimethylsilylethynyl CO.sub.2H 1-39 NH.sub.2 2-chloroethynyl CO.sub.2H 1-40 NH.sub.2 2-bromoethynyl CO.sub.2H 1-41 NH.sub.2 methyl CO.sub.2Me 1-42 NH.sub.2 ethyl CO.sub.2Me 1-43 NH.sub.2 n-propyl CO.sub.2Me 1-44 NH.sub.2 isopropyl CO.sub.2Me 1-45 NH.sub.2 difluoromethyl CO.sub.2Me 1-46 NH.sub.2 trifluoromethyl CO.sub.2Me 1-47 NH.sub.2 hydroxymethyl CO.sub.2Me 1-48 NH.sub.2 methoxymethyl CO.sub.2Me 1-49 NH.sub.2 1-hydroxyethyl CO.sub.2Me 1-50 NH.sub.2 2-hydroxyethyl CO.sub.2Me 1-51 NH.sub.2 2-methoxyethyl CO.sub.2Me 1-52 NH.sub.2 formyl CO.sub.2Me 1-53 NH.sub.2 acetyl CO.sub.2Me 1-54 NH.sub.2 hydroxyiminomethyl CO.sub.2Me 1-55 NH.sub.2 methoxyiminomethyl CO.sub.2Me 1-56 NH.sub.2 1-(hydroxyimino)ethyl CO.sub.2Me 1-57 NH.sub.2 1-(methoxyimino)ethyl CO.sub.2Me 1-58 NH.sub.2 cyclopropyl CO.sub.2Me 1-59 NH.sub.2 1-methylcyclopropyl CO.sub.2Me 1-60 NH.sub.2 2,2-dichlorocyclopropyl CO.sub.2Me 1-61 NH.sub.2 vinyl CO.sub.2Me 1-62 NH.sub.2 prop-1-enyl CO.sub.2Me 1-63 NH.sub.2 prop-2-enyl CO.sub.2Me 1-64 NH.sub.2 prop-1-en-2-yl CO.sub.2Me 1-65 NH.sub.2 pent-1-enyl CO.sub.2Me 1-66 NH.sub.2 2-cyclopropylvinyl CO.sub.2Me 1-67 NH.sub.2 1-ethoxyvinyl CO.sub.2Me 1-68 NH.sub.2 1-methylprop-1-enyl CO.sub.2Me 1-69 NH.sub.2 2-methylprop-1-enyl CO.sub.2Me 1-70 NH.sub.2 1,2-dimethylprop-1-enyl CO.sub.2Me 1-71 NH.sub.2 2,2-dichlorovinyl CO.sub.2Me 1-72 NH.sub.2 3-methylbut-2-enyl CO.sub.2Me 1-73 NH.sub.2 ethynyl CO.sub.2Me 1-74 NH.sub.2 prop-1-ynyl CO.sub.2Me 1-75 NH.sub.2 but-1-ynyl CO.sub.2Me 1-76 NH.sub.2 3-methylbut-1-ynyl CO.sub.2Me 1-77 NH.sub.2 3,3-dimethylbut-1-ynyl CO.sub.2Me 1-78 NH.sub.2 2-trimethylsilylethynyl CO.sub.2Me 1-79 NH.sub.2 2-chloroethynyl CO.sub.2Me 1-80 NH.sub.2 2-bromoethynyl CO.sub.2Me 1-81 NH.sub.2 methyl CO.sub.2Et 1-82 NH.sub.2 ethyl CO.sub.2Et 1-83 NH.sub.2 n-propyl CO.sub.2Et 1-84 NH.sub.2 isopropyl CO.sub.2Et 1-85 NH.sub.2 difluoromethyl CO.sub.2Et 1-86 NH.sub.2 trifluoromethyl CO.sub.2Et 1-87 NH.sub.2 hydroxymethyl CO.sub.2Et 1-88 NH.sub.2 methoxymethyl CO.sub.2Et 1-89 NH.sub.2 1-hydroxyethyl CO.sub.2Et 1-90 NH.sub.2 2-hydroxyethyl CO.sub.2Et 1-91 NH.sub.2 2-methoxyethyl CO.sub.2Et 1-92 NH.sub.2 formyl CO.sub.2Et 1-93 NH.sub.2 acetyl CO.sub.2Et 1-94 NH.sub.2 hydroxyiminomethyl CO.sub.2Et 1-95 NH.sub.2 methoxyiminomethyl CO.sub.2Et 1-96 NH.sub.2 1-(hydroxyimino)ethyl CO.sub.2Et 1-97 NH.sub.2 1-(methoxyimino)ethyl CO.sub.2Et 1-98 NH.sub.2 cyclopropyl CO.sub.2Et 1-99 NH.sub.2 1-methylcyclopropyl CO.sub.2Et 1-100 NH.sub.2 2,2-dichlorocyclopropyl CO.sub.2Et 1-101 NH.sub.2 vinyl CO.sub.2Et 1-102 NH.sub.2 prop-1-enyl CO.sub.2Et 1-103 NH.sub.2 prop-2-enyl CO.sub.2Et 1-104 NH.sub.2 prop-1-en-2-yl CO.sub.2Et 1-105 NH.sub.2 pent-1-enyl CO.sub.2Et 1-106 NH.sub.2 2-cyclopropylvinyl CO.sub.2Et 1-107 NH.sub.2 1-ethoxyvinyl CO.sub.2Et 1-108 NH.sub.2 1-methylprop-1-enyl CO.sub.2Et 1-109 NH.sub.2 2-methylprop-1-enyl CO.sub.2Et 1-110 NH.sub.2 1,2-dimethylprop-1-enyl CO.sub.2Et 1-111 NH.sub.2 2,2-dichlorovinyl CO.sub.2Et 1-112 NH.sub.2 3-methylbut-2-enyl CO.sub.2Et 1-113 NH.sub.2 ethynyl CO.sub.2Et 1-114 NH.sub.2 prop-1-ynyl CO.sub.2Et 1-115 NH.sub.2 but-1-ynyl CO.sub.2Et 1-116 NH.sub.2 3-methylbut-1-ynyl CO.sub.2Et 1-117 NH.sub.2 3,3-dimethylbut-1-ynyl CO.sub.2Et 1-118 NH.sub.2 2-trimethylsilylethynyl CO.sub.2Et 1-119 NH.sub.2 2-chloroethynyl CO.sub.2Et 1-120 NH.sub.2 2-bromoethynyl CO.sub.2Et 1-121 NHMe methyl CO.sub.2H 1-122 NHMe trifluoromethyl CO.sub.2H 1-123 NHMe acetyl CO.sub.2H 1-124 NHMe cyclopropyl CO.sub.2H 1-125 NHMe vinyl CO.sub.2H 1-126 NHMe prop-1-enyl CO.sub.2H 1-127 NHMe prop-2-enyl CO.sub.2H 1-128 NHMe ethynyl CO.sub.2H 1-129 NHMe prop-1-ynyl CO.sub.2H 1-130 NHMe 2-trimethylsilylethynyl CO.sub.2H 1-131 NMe.sub.2 methyl CO.sub.2H 1-132 NMe.sub.2 trifluoromethyl CO.sub.2H 1-133 NMe.sub.2 acetyl CO.sub.2H 1-134 NMe.sub.2 cyclopropyl CO.sub.2H 1-135 NMe.sub.2 vinyl CO.sub.2H 1-136 NMe.sub.2 prop-1-enyl CO.sub.2H 1-137 NMe.sub.2 prop-2-enyl CO.sub.2H 1-138 NMe.sub.2 ethynyl CO.sub.2H 1-139 NMe.sub.2 prop-1-ynyl CO.sub.2H 1-140 NMe.sub.2 2-trimethylsilylethynyl CO.sub.2H 1-141 NHCOMe methyl CO.sub.2H 1-142 NHCOMe trifluoromethyl CO.sub.2H 1-143 NHCOMe acetyl CO.sub.2H 1-144 NHCOMe cyclopropyl CO.sub.2H 1-145 NHCOMe vinyl CO.sub.2H 1-146 NHCOMe prop-1-enyl CO.sub.2H 1-147 NHCOMe prop-2-enyl CO.sub.2H 1-148 NHCOMe ethynyl CO.sub.2H 1-149 NHCOMe prop-1-ynyl CO.sub.2H 1-150 NHCOMe 2-trimethylsilylethynyl CO.sub.2H 1-151 NHCO.sub.2Me methyl CO.sub.2H 1-152 NHCO.sub.2Me trifluoromethyl CO.sub.2H 1-153 NHCO.sub.2Me acetyl CO.sub.2H 1-154 NHCO.sub.2Me cyclopropyl CO.sub.2H 1-155 NHCO.sub.2Me vinyl CO.sub.2H 1-156 NHCO.sub.2Me prop-1-enyl CO.sub.2H 1-157 NHCO.sub.2Me prop-2-enyl CO.sub.2H 1-158 NHCO.sub.2Me ethynyl CO.sub.2H 1-159 NHCO.sub.2Me prop-1-ynyl CO.sub.2H 1-160 NHCO.sub.2Me 2-trimethylsilylethynyl CO.sub.2H 1-161 NHSO.sub.2Me methyl CO.sub.2H 1-162 NHSO.sub.2Me trifluoromethyl CO.sub.2H 1-163 NHSO.sub.2Me acetyl CO.sub.2H 1-164 NHSO.sub.2Me cyclopropyl CO.sub.2H 1-165 NHSO.sub.2Me vinyl CO.sub.2H 1-166 NHSO.sub.2Me prop-1-enyl CO.sub.2H 1-167 NHSO.sub.2Me prop-2-enyl CO.sub.2H 1-168 NHSO.sub.2Me ethynyl CO.sub.2H 1-169 NHSO.sub.2Me prop-1-ynyl CO.sub.2H 1-170 NHSO.sub.2Me 2-trimethylsilylethynyl CO.sub.2H 1-171 NMeCOMe methyl CO.sub.2H 1-172 NMeCOMe trifluoromethyl CO.sub.2H 1-173 NMeCOMe acetyl CO.sub.2H 1-174 NMeCOMe cyclopropyl CO.sub.2H 1-175 NMeCOMe vinyl CO.sub.2H 1-176 NMeCOMe prop-1-enyl CO.sub.2H 1-177 NMeCOMe prop-2-enyl CO.sub.2H 1-178 NMeCOMe ethynyl CO.sub.2H 1-179 NMeCOMe prop-1-ynyl CO.sub.2H 1-180 NMeCOMe 2-trimethylsilylethynyl CO.sub.2H 1-181 NMeCO.sub.2Me methyl CO.sub.2H 1-182 NMeCO.sub.2Me trifluoromethyl CO.sub.2H 1-183 NMeCO.sub.2Me acetyl CO.sub.2H 1-184 NMeCO.sub.2Me cyclopropyl CO.sub.2H 1-185 NMeCO.sub.2Me vinyl CO.sub.2H 1-186 NMeCO.sub.2Me prop-1-enyl CO.sub.2H 1-187 NMeCO.sub.2Me prop-2-enyl CO.sub.2H 1-188 NMeCO.sub.2Me ethynyl CO.sub.2H 1-189 NMeCO.sub.2Me prop-1-ynyl CO.sub.2H 1-190 NMeCO.sub.2Me 2-trimethylsilylethynyl CO.sub.2H 1-191 NMeSO.sub.2Me methyl CO.sub.2H 1-192 NMeSO.sub.2Me trifluoromethyl CO.sub.2H 1-193 NMeSO.sub.2Me acetyl CO.sub.2H 1-194 NMeSO.sub.2Me cyclopropyl CO.sub.2H 1-195 NMeSO.sub.2Me vinyl CO.sub.2H 1-196 NMeSO.sub.2Me prop-1-enyl CO.sub.2H 1-197 NMeSO.sub.2Me prop-2-enyl CO.sub.2H 1-198 NMeSO.sub.2Me ethynyl CO.sub.2H 1-199 NMeSO.sub.2Me prop-1-ynyl CO.sub.2H 1-200 NMeSO.sub.2Me 2-trimethylsilylethynyl CO.sub.2H 1-201 NH.sup.iPr methyl CO.sub.2H 1-202 NH.sup.iPr trifluoromethyl CO.sub.2H 1-203 NH.sup.iPr acetyl CO.sub.2H 1-204 NH.sup.iPr cyclopropyl CO.sub.2H 1-205 NH.sup.iPr vinyl CO.sub.2H 1-206 NH.sup.iPr prop-1-enyl CO.sub.2H 1-207 NH.sup.iPr prop-2-enyl CO.sub.2H 1-208 NH.sup.iPr ethynyl CO.sub.2H 1-209 NH.sup.iPr prop-1-ynyl CO.sub.2H 1-210 NH.sup.iPr 2-trimethylsilylethynyl CO.sub.2H 1-211 NHMe methyl CO.sub.2Me 1-212 NHMe trifluoromethyl CO.sub.2Me 1-213 NHMe acetyl CO.sub.2Me 1-214 NHMe cyclopropyl CO.sub.2Me 1-215 NHMe vinyl CO.sub.2Me 1-216 NHMe prop-1-enyl CO.sub.2Me 1-217 NHMe prop-2-enyl CO.sub.2Me 1-218 NHMe ethynyl CO.sub.2Me 1-219 NHMe prop-1-ynyl CO.sub.2Me 1-220 NHMe 2-trimethylsilylethynyl CO.sub.2Me 1-221 NMe.sub.2 methyl CO.sub.2Me 1-222 NMe.sub.2 trifluoromethyl CO.sub.2Me 1-223 NMe.sub.2 acetyl CO.sub.2Me 1-224 NMe.sub.2 cyclopropyl CO.sub.2Me 1-225 NMe.sub.2 vinyl CO.sub.2Me 1-226 NMe.sub.2 prop-1-enyl CO.sub.2Me 1-227 NMe.sub.2 prop-2-enyl CO.sub.2Me 1-228 NMe.sub.2 ethynyl CO.sub.2Me 1-229 NMe.sub.2 prop-1-ynyl CO.sub.2Me 1-230 NMe.sub.2 2-trimethylsilylethynyl CO.sub.2Me 1-231 NHCOMe methyl CO.sub.2Me 1-232 NHCOMe trifluoromethyl CO.sub.2Me 1-233 NHCOMe acetyl CO.sub.2Me 1-234 NHCOMe cyclopropyl CO.sub.2Me 1-235 NHCOMe vinyl CO.sub.2Me 1-236 NHCOMe prop-1-enyl CO.sub.2Me 1-237 NHCOMe prop-2-enyl CO.sub.2Me 1-238 NHCOMe ethynyl CO.sub.2Me 1-239 NHCOMe prop-1-ynyl CO.sub.2Me 1-240 NHCOMe 2-trimethylsilylethynyl CO.sub.2Me 1-241 NHCO.sub.2Me methyl CO.sub.2Me 1-242 NHCO.sub.2Me trifluoromethyl CO.sub.2Me 1-243 NHCO.sub.2Me acetyl CO.sub.2Me 1-244 NHCO.sub.2Me cyclopropyl CO.sub.2Me 1-245 NHCO.sub.2Me vinyl CO.sub.2Me

1-246 NHCO.sub.2Me prop-1-enyl CO.sub.2Me 1-247 NHCO.sub.2Me prop-2-enyl CO.sub.2Me 1-248 NHCO.sub.2Me ethynyl CO.sub.2Me 1-249 NHCO.sub.2Me prop-1-ynyl CO.sub.2Me 1-250 NHCO.sub.2Me 2-trimethylsilylethynyl CO.sub.2Me 1-251 NHSO.sub.2Me methyl CO.sub.2Me 1-252 NHSO.sub.2Me trifluoromethyl CO.sub.2Me 1-253 NHSO.sub.2Me acetyl CO.sub.2Me 1-254 NHSO.sub.2Me cyclopropyl CO.sub.2Me 1-255 NHSO.sub.2Me vinyl CO.sub.2Me 1-256 NHSO.sub.2Me prop-1-enyl CO.sub.2Me 1-257 NHSO.sub.2Me prop-2-enyl CO.sub.2Me 1-258 NHSO.sub.2Me ethynyl CO.sub.2Me 1-259 NHSO.sub.2Me prop-1-ynyl CO.sub.2Me 1-260 NHSO.sub.2Me 2-trimethylsilylethynyl CO.sub.2Me 1-261 NMeCOMe methyl CO.sub.2Me 1-262 NMeCOMe trifluoromethyl CO.sub.2Me 1-263 NMeCOMe acetyl CO.sub.2Me 1-264 NMeCOMe cyclopropyl CO.sub.2Me 1-265 NMeCOMe vinyl CO.sub.2Me 1-266 NMeCOMe prop-1-enyl CO.sub.2Me 1-267 NMeCOMe prop-2-enyl CO.sub.2Me 1-268 NMeCOMe ethynyl CO.sub.2Me 1-269 NMeCOMe prop-1-ynyl CO.sub.2Me 1-270 NMeCOMe 2-trimethylsilylethynyl CO.sub.2Me 1-271 NMeCO.sub.2Me methyl CO.sub.2Me 1-272 NMeCO.sub.2Me trifluoromethyl CO.sub.2Me 1-273 NMeCO.sub.2Me acetyl CO.sub.2Me 1-274 NMeCO.sub.2Me cyclopropyl CO.sub.2Me 1-275 NMeCO.sub.2Me vinyl CO.sub.2Me 1-276 NMeCO.sub.2Me prop-1-enyl CO.sub.2Me 1-277 NMeCO.sub.2Me prop-2-enyl CO.sub.2Me 1-278 NMeCO.sub.2Me ethynyl CO.sub.2Me 1-279 NMeCO.sub.2Me prop-1-ynyl CO.sub.2Me 1-280 NMeCO.sub.2Me 2-trimethylsilylethynyl CO.sub.2Me 1-281 NMeSO.sub.2Me methyl CO.sub.2Me 1-282 NMeSO.sub.2Me trifluoromethyl CO.sub.2Me 1-283 NMeSO.sub.2Me acetyl CO.sub.2Me 1-284 NMeSO.sub.2Me cyclopropyl CO.sub.2Me 1-285 NMeSO.sub.2Me vinyl CO.sub.2Me 1-286 NMeSO.sub.2Me prop-1-enyl CO.sub.2Me 1-287 NMeSO.sub.2Me prop-2-enyl CO.sub.2Me 1-288 NMeSO.sub.2Me ethynyl CO.sub.2Me 1-289 NMeSO.sub.2Me prop-1-ynyl CO.sub.2Me 1-290 NMeSO.sub.2Me 2-trimethylsilylethynyl CO.sub.2Me 1-291 NH.sup.iPr methyl CO.sub.2Me 1-292 NH.sup.iPr trifluoromethyl CO.sub.2Me 1-293 NH.sup.iPr acetyl CO.sub.2Me 1-294 NH.sup.iPr cyclopropyl CO.sub.2Me 1-295 NH.sup.iPr vinyl CO.sub.2Me 1-296 NH.sup.iPr prop-1-enyl CO.sub.2Me 1-297 NH.sup.iPr prop-2-enyl CO.sub.2Me 1-298 NH.sup.iPr ethynyl CO.sub.2Me 1-299 NH.sup.iPr prop-1-ynyl CO.sub.2Me 1-300 NH.sup.iPr 2-trimethylsilylethynyl CO.sub.2Me 1-301 NMe.sub.2 methyl CO.sub.2Et 1-302 NH.sub.2 methyl CO.sub.2.sup.iPr 1-303 NH.sub.2 trifluoromethyl CO.sub.2.sup.iPr 1-304 NH.sub.2 acetyl CO.sub.2.sup.iPr 1-305 NH.sub.2 cyclopropyl CO.sub.2.sup.iPr 1-306 NH.sub.2 vinyl CO.sub.2.sup.iPr 1-307 NH.sub.2 prop-1-enyl CO.sub.2.sup.iPr 1-308 NH.sub.2 prop-2-enyl CO.sub.2.sup.iPr 1-309 NH.sub.2 ethynyl CO.sub.2.sup.iPr 1-310 NH.sub.2 prop-1-ynyl CO.sub.2.sup.iPr 1-311 NH.sub.2 2-trimethylsilylethynyl CO.sub.2.sup.iPr 1-312 NH.sub.2 methyl CO.sub.2.sup.nPr 1-313 NH.sub.2 trifluoromethyl CO.sub.2.sup.nPr 1-314 NH.sub.2 acetyl CO.sub.2.sup.nPr 1-315 NH.sub.2 cyclopropyl CO.sub.2.sup.nPr 1-316 NH.sub.2 vinyl CO.sub.2.sup.nPr 1-317 NH.sub.2 prop-1-enyl CO.sub.2.sup.nPr 1-318 NH.sub.2 prop-2-enyl CO.sub.2.sup.nPr 1-319 NH.sub.2 ethynyl CO.sub.2.sup.nPr 1-320 NH.sub.2 prop-1-ynyl CO.sub.2.sup.nPr 1-321 NH.sub.2 2-trimethylsilylethynyl CO.sub.2.sup.nPr 1-322 NH.sub.2 methyl CO.sub.2CH.sub.2.sup.iPr 1-323 NH.sub.2 trifluoromethyl CO.sub.2CH.sub.2.sup.iPr 1-324 NH.sub.2 acetyl CO.sub.2CH.sub.2.sup.iPr 1-325 NH.sub.2 cyclopropyl CO.sub.2CH.sub.2.sup.iPr 1-326 NH.sub.2 vinyl CO.sub.2CH.sub.2.sup.iPr 1-327 NH.sub.2 prop-1-enyl CO.sub.2CH.sub.2.sup.iPr 1-328 NH.sub.2 prop-2-enyl CO.sub.2CH.sub.2.sup.iPr 1-329 NH.sub.2 ethynyl CO.sub.2CH.sub.2.sup.iPr 1-330 NH.sub.2 prop-1-ynyl CO.sub.2CH.sub.2.sup.iPr 1-331 NH.sub.2 2-trimethylsilylethynyl CO.sub.2CH.sub.2.sup.iPr 1-332 NH.sub.2 methyl CO.sub.2CH.sub.2Ph 1-333 NH.sub.2 trifluoromethyl CO.sub.2CH.sub.2Ph 1-334 NH.sub.2 acetyl CO.sub.2CH.sub.2Ph 1-335 NH.sub.2 cyclopropyl CO.sub.2CH.sub.2Ph 1-336 NH.sub.2 vinyl CO.sub.2CH.sub.2Ph 1-337 NH.sub.2 prop-1-enyl CO.sub.2CH.sub.2Ph 1-338 NH.sub.2 prop-2-enyl CO.sub.2CH.sub.2Ph 1-339 NH.sub.2 ethynyl CO.sub.2CH.sub.2Ph 1-340 NH.sub.2 prop-1-ynyl CO.sub.2CH.sub.2Ph 1-341 NH.sub.2 2-trimethylsilylethynyl CO.sub.2CH.sub.2Ph 1-342 NH.sub.2 methyl CONH.sub.2 1-343 NH.sub.2 trifluoromethyl CONH.sub.2 1-344 NH.sub.2 acetyl CONH.sub.2 1-345 NH.sub.2 cyclopropyl CONH.sub.2 1-346 NH.sub.2 vinyl CONH.sub.2 1-347 NH.sub.2 prop-1-enyl CONH.sub.2 1-348 NH.sub.2 prop-2-enyl CONH.sub.2 1-349 NH.sub.2 ethynyl CONH.sub.2 1-350 NH.sub.2 prop-1-ynyl CONH.sub.2 1-351 NH.sub.2 2-trimethylsilylethynyl CONH.sub.2 1-352 NH.sub.2 methyl OCH.sub.2CO.sub.2H 1-353 NH.sub.2 trifluoromethyl OCH.sub.2CO.sub.2H 1-354 NH.sub.2 acetyl OCH.sub.2CO.sub.2H 1-355 NH.sub.2 cyclopropyl OCH.sub.2CO.sub.2H 1-356 NH.sub.2 vinyl OCH.sub.2CO.sub.2H 1-357 NH.sub.2 prop-1-enyl OCH.sub.2CO.sub.2H 1-358 NH.sub.2 prop-2-enyl OCH.sub.2CO.sub.2H 1-359 NH.sub.2 ethynyl OCH.sub.2CO.sub.2H 1-360 NH.sub.2 prop-1-ynyl OCH.sub.2CO.sub.2H 1-361 NH.sub.2 2-trimethylsilylethynyl OCH.sub.2CO.sub.2H 1-362 NH.sub.2 methyl OCH.sub.2CO.sub.2Me 1-363 NH.sub.2 trifluoromethyl OCH.sub.2CO.sub.2Me 1-364 NH.sub.2 acetyl OCH.sub.2CO.sub.2Me 1-365 NH.sub.2 cyclopropyl OCH.sub.2CO.sub.2Me 1-366 NH.sub.2 vinyl OCH.sub.2CO.sub.2Me 1-367 NH.sub.2 prop-1-enyl OCH.sub.2CO.sub.2Me 1-368 NH.sub.2 prop-2-enyl OCH.sub.2CO.sub.2Me 1-369 NH.sub.2 ethynyl OCH.sub.2CO.sub.2Me 1-370 NH.sub.2 prop-1-ynyl OCH.sub.2CO.sub.2Me 1-371 NH.sub.2 2-trimethylsilylethynyl OCH.sub.2CO.sub.2Me 1-372 NH.sub.2 1-hydroxyethyl CH.sub.2OH 1-373 Cl methyl CO.sub.2H 1-374 Cl methyl CO.sub.2Me 1-375 Cl methyl OCH.sub.2CO.sub.2H 1-376 Cl methyl OCH.sub.2CO.sub.2Me 1-377 OMe methyl CO.sub.2H 1-378 OMe methyl CO.sub.2Me 1-379 OMe methyl OCH.sub.2CO.sub.2H 1-380 OMe methyl OCH.sub.2CO.sub.2Me 1-381 OCH.sub.2CO.sub.2Me methyl CO.sub.2H 1-382 OCH.sub.2CO.sub.2Me methyl CO.sub.2Me 1-383 OCH.sub.2CO.sub.2Me methyl OCH.sub.2CO.sub.2H 1-384 OCH.sub.2CO.sub.2Me methyl OCH.sub.2CO.sub.2Me 1-385 N.sub.3 methyl CO.sub.2H 1-386 N.sub.3 methyl CO.sub.2Me 1-387 N.sub.3 methyl OCH.sub.2CO.sub.2H 1-388 N.sub.3 methyl OCH.sub.2CO.sub.2Me 1-389 OCH.sub.2CO.sub.2.sup.tBu methyl OCH.sub.2CO.sub.2.sup.tBu 1-390 Cl methyl CO.sub.2Et 1-391 NH.sub.2 vinyl CO.sub.2.sup.nBu 1-392 NH.sub.2 vinyl CO.sub.2.sup.noctyl 1-393 NH.sub.2 vinyl CO.sub.2(2-ethylhexyl) 1-394 NH.sub.2 vinyl CO.sub.2CH(Me)Ph 1-395 NH.sub.2 vinyl CO.sub.2prop-2-enyl 1-396 NH.sub.2 vinyl CO.sub.2(CH.sub.2).sub.2OEt 1-397 NH.sub.2 vinyl CO.sub.2(CH.sub.2).sub.2O.sup.nBu 1-398 OMe vinyl CO.sub.2Me 1-399 N.sub.3 vinyl CO.sub.2Me 1-400 SMe vinyl CO.sub.2Me 1-401 SOMe vinyl CO.sub.2Me 1-402 SO.sub.2Me vinyl CO.sub.2Me

[0139] 402 compounds of formula (I), wherein A is cyclopropyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 2-1 to 2-402, respectively.

[0140] 402 compounds of formula (I), wherein A is 2-methylcyclopropyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 3-1 to 3-402, respectively.

[0141] 402 compounds of formula (I), wherein A is isopropyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 4-1 to 4-402, respectively.

[0142] 402 compounds of formula (I), wherein A is 4-chlorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 5-1 to 5-402, respectively.

[0143] 402 compounds of formula (I), wherein A is 4-bromophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 6-1 to 6-402, respectively.

[0144] 402 compounds of formula (I), wherein A is 4-iodophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 7-1 to 7-402, respectively.

[0145] 402 compounds of formula (I), wherein A is 2,4-dichlorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 8-1 to 8-402, respectively.

[0146] 402 compounds of formula (I), wherein A is 3,4-dichlorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 9-1 to 9-402, respectively.

[0147] 402 compounds of formula (I), wherein A is 4-chloro-2-methylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 10-1 to 10-402, respectively.

[0148] 402 compounds of formula (I), wherein A is 4-chloro-2-methoxyphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 11-1 to 11-402, respectively.

[0149] 402 compounds of formula (I), wherein A is 4-chloro-2,6-difluorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 12-1 to 12-402, respectively.

[0150] 402 compounds of formula (I), wherein A is 4-chloro-3-methylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 13-1 to 13-402, respectively.

[0151] 402 compounds of formula (I), wherein A is 4-chloro-3-trifluoromethylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 14-1 to 14-402, respectively.

[0152] 402 compounds of formula (I), wherein A is 4-chloro-2-fluorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 15-1 to 15-402, respectively.

[0153] 402 compounds of formula (I), wherein A is 4-chloro-3-nitrophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 16-1 to 16-402, respectively.

[0154] 402 compounds of formula (I), wherein A is 4-chloro-2-trifluoromethylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 17-1 to 17-402, respectively.

[0155] 402 compounds of formula (I), wherein A is 4-chloro-3-cyanophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 18-1 to 18-402, respectively.

[0156] 402 compounds of formula (I), wherein A is 4-chloro-3-fluorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 19-1 to 19-402, respectively.

[0157] 402 compounds of formula (I), wherein A is 2,4,6-trichlorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 20-1 to 20-402, respectively.

[0158] 402 compounds of formula (I), wherein A is 2,4-dichloro-3-fluorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 21-1 to 21-402, respectively.

[0159] 402 compounds of formula (I), wherein A is 4-chloro-2,3-difluorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 22-1 to 22-402, respectively.

[0160] 402 compounds of formula (I), wherein A is 3,4-dichloro-2-fluorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 23-1 to 23-402, respectively.

[0161] 402 compounds of formula (I), wherein A is 2,4-dichloro-6-fluorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 24-1 to 24-402, respectively.

[0162] 402 compounds of formula (I), wherein A is 2,4,5-trichlorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 25-1 to 25-402, respectively.

[0163] 402 compounds of formula (I), wherein A is 4-chloro-3-methoxyphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 26-1 to 26-402, respectively.

[0164] 402 compounds of formula (I), wherein A is 4-chloro-2-fluoro-3-methoxyphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 27-1 to 27-402, respectively.

[0165] 402 compounds of formula (I), wherein A is 4-chloro-2-fluoro-3-trifluoromethylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 28-1 to 28-402, respectively.

[0166] 402 compounds of formula (I), wherein A is 2,3,4-trichlorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 29-1 to 29-402, respectively.

[0167] 402 compounds of formula (I), wherein A is 4-chloro-3,5-difluorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 30-1 to 30-402, respectively.

[0168] 402 compounds of formula (I), wherein A is 4-trifluoromethylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 31-1 to 31-402, respectively.

[0169] 402 compounds of formula (I), wherein A is 2,4-bis(trifluoromethyl)phenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 32-1 to 32-402, respectively.

[0170] 402 compounds of formula (I), wherein A is 4-chloro-3-dimethylamino-2-fluorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 33-1 to 33-402, respectively.

[0171] 402 compounds of formula (I), wherein A is 3-chloro-4-trifluoromethylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 34-1 to 34-402, respectively.

[0172] 402 compounds of formula (I), wherein A is 2-chloro-4-trifluoromethylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 35-1 to 35-402, respectively.

[0173] 402 compounds of formula (I), wherein A is 4-methylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 36-1 to 36-402, respectively.

[0174] 402 compounds of formula (I), wherein A is 2-chloro-4-methylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 37-1 to 37-402, respectively.

[0175] 402 compounds of formula (I), wherein A is 3-chloro-4-methylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 38-1 to 38-402, respectively.

[0176] 402 compounds of formula (I), wherein A is 3-fluoro-4-methylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 39-1 to 39-402, respectively.

[0177] 402 compounds of formula (I), wherein A is 2,4,5-trimethylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 40-1 to 40-402, respectively.

[0178] 402 compounds of formula (I), wherein A is 4-fluorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 41-1 to 41-402, respectively.

[0179] 402 compounds of formula (I), wherein A is 4-fluoro-3-methoxyphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 42-1 to 42-402, respectively.

[0180] 402 compounds of formula (I), wherein A is 4-fluoro-3-trifluoromethylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 43-1 to 43-402, respectively.

[0181] 402 compounds of formula (I), wherein A is 3-chloro-4-fluorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 44-1 to 44-402, respectively.

[0182] 402 compounds of formula (I), wherein A is 4-fluoro-3-methylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 45-1 to 45-402, respectively.

[0183] 402 compounds of formula (I), wherein A is 2,3,4-trifluorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 46-1 to 46-402, respectively.

[0184] 402 compounds of formula (I), wherein A is 4-trifluoromethoxyphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 47-1 to 47-402, respectively.

[0185] 402 compounds of formula (I), wherein A is 2-fluoro-3-methoxyphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 48-1 to 48-402, respectively.

[0186] 402 compounds of formula (I), wherein A is 4-methoxyphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 49-1 to 49-402, respectively.

[0187] 402 compounds of formula (I), wherein A is 4-methoxy-2-methylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 50-1 to 50-402, respectively.

[0188] 402 compounds of formula (I), wherein A is 2,4-dimethoxyphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 51-1 to 51-402, respectively.

[0189] 402 compounds of formula (I), wherein A is 3-fluoro-4-methoxyphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 52-1 to 52-402, respectively.

[0190] 402 compounds of formula (I), wherein A is 3-chloro-4-methoxyphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 53-1 to 53-402, respectively.

[0191] 402 compounds of formula (I), wherein A is 3,4-dimethylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 54-1 to 54-402, respectively.

[0192] 402 compounds of formula (I), wherein A is 4-methyl-3-nitrophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 55-1 to 55-402, respectively.

[0193] 402 compounds of formula (I), wherein A is 2-fluoro-4-methylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 56-1 to 56-402, respectively.

[0194] 402 compounds of formula (I), wherein A is 2-fluoro-4-methoxyphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 57-1 to 57-402, respectively.

[0195] 402 compounds of formula (I), wherein A is 2,3,4-trimethoxyphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 58-1 to 58-402, respectively.

[0196] 402 compounds of formula (I), wherein A is 3,4-dimethoxyphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 59-1 to 59-402, respectively.

[0197] 402 compounds of formula (I), wherein A is 2-fluoro-3-methoxy-4-methylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 60-1 to 60-402, respectively.

[0198] 402 compounds of formula (I), wherein A is 3-chloro-5-fluorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 61-1 to 61-402, respectively.

[0199] 402 compounds of formula (I), wherein A is methylthio, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 62-1 to 62-402, respectively.

[0200] 402 compounds of formula (I), wherein A is 3,4,5-trifluorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 63-1 to 63-402, respectively.

[0201] 402 compounds of formula (I), wherein A is 3-dimethylamino-4-ethenyl-2-fluorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 64-1 to 64-402, respectively.

[0202] 402 compounds of formula (I), wherein A is 4-acetyl-2-fluoro-3-methoxyphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 65-1 to 65-402, respectively.

[0203] 402 compounds of formula (I), wherein A is 4-(1-ethoxyethenyl)-2-fluoro-3-methoxyphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 66-1 to 66-402, respectively.

[0204] 402 compounds of formula (I), wherein A is 3,4-difluorophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 67-1 to 67-402, respectively.

[0205] 402 compounds of formula (I), wherein A is 4-cyanophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 68-1 to 68-402, respectively.

[0206] 402 compounds of formula (I), wherein A is 4-methoxycarbonylphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 69-1 to 69-402, respectively.

[0207] 402 compounds of formula (I), wherein A is 3,4-methylenedioxyphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 70-1 to 70-402, respectively.

[0208] 402 compounds of formula (I), wherein A is 3,4-ethylenedioxyphenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 71-1 to 71-402, respectively.

[0209] 402 compounds of formula (I), wherein A is 4-methylthiophenyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 72-1 to 72-402, respectively.

[0210] 402 compounds of formula (I), wherein A is 4-naphthyl, and the values of X, Y and Z are as given in Table 1 for compounds 1-1 to 1-402, are designated as compound Nos. 73-1 to 73-402, respectively.

[0211] General methods for the production of compounds of formula (I) are described below. Unless otherwise stated in the text, the substitutents A, X, Y and Z are as defined hereinbefore. The abbreviation LG as used herein refers to any suitable leaving group, and includes halogen, sulphonate, and sulphone groups. The groups R as used herein are, independently of each other, alkyl or substituted alkyl groups, preferably C1-C12 alkyl groups. The groups R' may, independently of each other, take a range of values depending on the particular structure of the molecule in which they are present; the skilled man will recognise what values are applicable in each case, particularly in view of the definition of compounds of formula (I) as described hereinbefore.

[0212] Compounds of formula (I) may be prepared from compounds of formula (A), where LG represents a suitable leaving group (reaction scheme 1).

##STR00008##

[0213] For example, a compound of formula (I) may be prepared by reacting a suitable metal or metalloid derivative A-M (for example, a boronic acid or ester, a trialkyltin derivative, a zinc derivative or a Grignard reagent) with a compound of formula (A) in the presence of a suitable base (for example an inorganic base, such as potassium phosphate or caesium fluoride, or an organic base, such as triethylamine), a metal source (for example, a palladium source such as Pd.sub.2(dba).sub.3) and, optionally, a ligand for the metal (for example a phosphine ligand, such as X-Phos) in a suitable solvent (for example a single solvent, such as acetonitrile, or a mixed solvent system, such as a mixture of dimethoxyethane and water)--see reaction scheme 2. The metal catalyst and ligands may also be added as a single, pre-formed, complex (for example a palladium/phosphine complex, such as palladium tetrakistriphenylphosphine, bis(triphenylphosphine)palladium dichloride or [1,1'-bis(diphenylphosphino)ferrocene] palladium dichloride).

##STR00009##

[0214] As an additional example (see reaction scheme 3) a compound of formula (I) in which A is an alkenyl group may be prepared using a Heck reaction in which the group A component containing the double bond may be reacted with a compound of formula (A) in the presence of a suitable metal catalyst (for example a palladium derivative, such as palladium acetate), optionally with a suitable ligand for the metal, and a suitable base (for example an inorganic base, such as potassium phosphate) in a suitable solvent (for example N-methylpyrrolidone).

##STR00010##

[0215] Alternatively, compounds of formula (I) may be prepared from compounds of formula (B), where M represents a suitable metal or metalloid derivative (for example a boronic acid or ester, a trialkyltin group, a suitably substituted silyl group, a zinc derivative or a magnesium halide) by reaction with a compound A-LG in which LG represents a leaving group such as a halogen atom or sulphonate (reaction scheme 4, below).

##STR00011##

[0216] For example, a compound of formula (I) may be prepared from a compound of formula B in which M is a boronic acid group by reaction with a compound A-LG in the presence of a metal catalyst (for example a palladium derivative such as Pd.sub.2(dba).sub.3), optionally with a suitable ligand (for example a phosphine such as X-Phos) and a base (for example potassium phosphate or caesium fluoride) in a suitable solvent.

[0217] Compounds of formula (B) may be prepared from other compounds of formula (B) using a transmetallation reaction. For example, a compound of formula (B) where M is a boronic acid may be prepared from a compound of formula (B) where M is a magnesium halide by reaction with a trialkylboronate, followed by hydrolysis (for example under acidic conditions).

[0218] Alternatively compounds of formula (B) may be prepared from compounds of formula (A), shown schematically below (reaction scheme 5).

##STR00012##

[0219] For example, a compound of formula (B) where M is a boronate ester or a trialkylstannane may be prepared from a compound of formula (A) by treating it with a suitable M-containing reagent (for example pinacolborane, bispinacolatodiboron, hexa-alkyldi-tin) in the presence of a metal catalyst (for example a palladium species, such as bis(diphenylphosphine)palladium dichloride) in a suitable solvent (for example dioxane).

[0220] Alternatively, a compound of formula (B) where M is a magnesium halide may be prepared from a compound of formula (A) by treatment with a suitable Grignard reagent (for example an isopropylmagnesium halide such as isopropylmagnesium chloride) in a suitable solvent.

[0221] Compounds of formula (A) may be prepared from compounds of formula (C) (reaction scheme 6), where LG' is a second leaving group, which may be the same as or different to LG.

##STR00013##

[0222] For example, a compound of formula (A) may be prepared from a compound of formula (C) by reaction with a reagent X--H or X.sup.- in a suitable solvent (for example an ether solvent, such as tetrahydrofuran, or a polar aprotic solvent, such as dimethylsulphoxide). The reagent X.sup.- may be generated in situ by addition of a suitable base to X--H, or it may be prepared separately and added as a suitable salt.

[0223] As an additional example a compound of formula (A) may be prepared from a compound of formula (C) by treatment with a reagent X--H in the presence of a suitable catalyst (for example a metal catalyst, such as a palladium source) and optionally a suitable ligand (for example a phosphine ligand, such as Josiphos) in a suitable solvent.

[0224] Compounds of formula (C1), which are compounds of formula (C) in which LG and LG' are the same and are, for example, a halogen atom or a sulphonate) may be prepared from compounds of formula (D) (see reaction scheme 7 below).

##STR00014##

[0225] For example, a compound of formula (C1) in which LG is a halogen atom may be prepared from a compound of formula (D) by treatment with a suitable reagent (for example a phosphoryl halide such as phosphorous oxychloride) and optionally a suitable base (for example an organic base, such as N,N-diethylaniline).

[0226] Compounds of formula (C2) (that is compounds of formula (C) in which LG and LG' are different) may be prepared from compounds of formula (E) in which B represents a suitable precursor group to LG' (reaction scheme 8).

##STR00015##

[0227] For example, a compound of formula (C2) in which LG' is a sulphone may be prepared from a compound of formula (E1), which is a compound of formula (E) in which B is a thioether group, by reaction with a suitable oxidising agent, for example a peracid such as meta-chloroperbenzoic acid) (reaction scheme 9).

##STR00016##

[0228] Compounds of formula (E) may be prepared from compounds of formula (C1) by treatment with a reagent B--H or B.

[0229] For example, a compound of formula (E1) may be prepared from a compound of formula (C1) by reaction with a thiol or thiolate anion, optionally in the presence of a suitable base, in a suitable solvent (see reaction scheme 10).

##STR00017##

[0230] Compounds of formula (D) may be prepared from compounds of formula (F) by reaction with a suitable source of electropositive Y (reaction scheme 11).

##STR00018##

[0231] For example a compound of formula (D) in which Y is an acyl group may be prepared from a compound of formula (F) by reaction with an acyl halide (for example acetyl chloride) in the presence of a Lewis acid (for example aluminium trichloride) in a suitable solvent (for example nitrobenzene).

[0232] Alternatively, compounds of formula (D) may be prepared from compounds of formula (G) where D represents a suitable reactive group (see reaction scheme 12 below). Examples of such a reactive group are halogen atoms and sulphonates.

##STR00019##

[0233] For example, such a transformation may be carried out by reaction with a metal or metalloid derivative of the group Y (for example a boronic acid or boronate ester) in the presence of a base (for example an inorganic base, such as potassium phosphate or caesium fluoride, or an organic base, such as triethylamine), a metal source (for example, a palladium source such as Pd.sub.2(dba).sub.3) and, optionally, a ligand for the metal (for example a phosphine ligand, such as X-Phos) in a suitable solvent (for example a single solvent, such as acetonitrile, or a mixed solvent system, such as a mixture of dimethoxyethane and water). The metal catalyst and ligands may also be added as a single, pre-formed, complex (for example a palladium/phosphine complex, such as palladium tetrakistriphenylphosphine, bis(triphenylphosphine)palladium dichloride or [1,1'-bis(diphenylphosphino)ferrocene] palladium dichloride).

[0234] Compounds of formula (G) may be prepared from compounds of formula (F) by reaction with a suitable source of electropositive D (reaction scheme 13).

##STR00020##

[0235] For example a compound of formula (G) in which D is a halogen may be prepared from a compound of formula (F) by reaction with an N-halosuccinimide (for example N-chlorosuccinimide) in a suitable solvent (for example dimethylformamide).

[0236] Compounds of formula (F) are well known in the literature, or can be made readily from compounds known in the literature by standard methods known to the skilled man.

[0237] Compounds of formula (I) may also be prepared from compounds of formula (H) where D represents a suitable reactive group (see reaction scheme 14 below). Examples of such a reactive group are halogen atoms and sulphonates.

##STR00021##

[0238] For example, such a transformation may be carried out by reaction with a metal or metalloid derivative of the group Y (for example a boronic acid or boronate ester) in the presence of a base (for example an inorganic base, such as potassium phosphate or caesium fluoride, or an organic base, such as triethylamine), a metal source (for example, a palladium source such as Pd.sub.2(dba).sub.3) and, optionally, a ligand for the metal (for example a phosphine ligand, such as X-Phos) in a suitable solvent (for example a single solvent, such as acetonitrile, or a mixed solvent system, such as a mixture of dimethoxyethane and water). The metal catalyst and ligands may also be added as a single, pre-formed, complex (for example a palladium/phosphine complex, such as palladium tetrakistriphenylphosphine, bis(triphenylphosphine)palladium dichloride or [1,1'-bis(diphenylphosphino)ferrocene] palladium dichloride).

[0239] Compounds of formula (H) may be prepared from compounds of formula (I) (reaction scheme 15), where LG represents a suitable leaving group. Examples of such leaving groups are halogen atoms, sulphonates and sulphones.

##STR00022##

[0240] For example, a compound of formula (H1), which is a compound of formula (H) in which A is an alkylthio group, may be prepared by reacting a compound of formula (I) with an alkanethiolate (for example sodium methanethiolate) in a suitable solvent (for example a polar solvent, such as methanol). See reaction scheme 16 below.

##STR00023##

[0241] In a further example, a compound of formula (H) may be prepared by reacting a suitable metal or metalloid derivative A-M (for example, a boronic acid or ester, a trialkyltin derivative, a zinc derivative or a Grignard reagent) with a compound of formula (i) in the presence of a suitable base (for example an inorganic base, such as potassium phosphate or caesium fluoride, or an organic base, such as triethylamine), a metal source (for example, a palladium source such as Pd.sub.2(dba).sub.3) and, optionally, a ligand for the metal (for example a phosphine ligand, such as X-Phos) in a suitable solvent (for example a single solvent, such as acetonitrile, or a mixed solvent system, such as a mixture of dimethoxyethane and water). See reaction scheme 17 below. The metal catalyst and ligands may also be added as a single, pre-formed, complex (for example a palladium/phosphine complex, such as palladium tetrakistriphenylphosphine, bis(triphenylphosphine)palladium dichloride or [1,1'-bis(diphenylphosphino)ferrocene] palladium dichloride).

##STR00024##

[0242] As an additional example, a compound of formula (H) in which A is an alkenyl group may be prepared using a Heck reaction in which the group A component containing the double bond may be reacted with a compound of formula (i) in the presence of a suitable metal catalyst (for example a palladium derivative, such as palladium acetate), optionally with a suitable ligand for the metal, and a suitable base (for example an inorganic base, such as potassium phosphate) in a suitable solvent (for example N-methylpyrrolidone); see reaction scheme 18.

##STR00025##

[0243] Compounds of formula (i) may be prepared from compounds of formula (J), where LG' is a second leaving group which may be the same as or different to LG (reaction scheme 19).

##STR00026##

[0244] For example, a compound of formula (i) may be prepared from a compound of formula (J) by reaction with a reagent X--H or X.sup.- in a suitable solvent (for example an ether solvent, such as tetrahydrofuran). The reagent X.sup.- may be generated in situ by addition of a suitable base to X--H, or it may be prepared separately and added as a suitable salt.

[0245] As a further example, a compound of formula (i) may be prepared from a compound of formula (J) by treatment with a reagent X--H in the presence of a suitable catalyst (for example a metal catalyst, such as a palladium source) and optionally a suitable ligand (for example a phosphine ligand, such as Josiphos) in a suitable solvent.

[0246] Compounds of formula (J1), which are compounds of formula (J) in which LG and LG' are the same and are, for example, a halogen atom or a sulphonate, may be prepared from compounds of formula (G) (see reaction scheme 20 below).

##STR00027##

[0247] For example, a compound of formula (J1) in which LG is a halogen atom may be prepared from a compound of formula (G) by treatment with a suitable reagent (for example a phosphoryl halide such as phosphorous oxychloride) and optionally a suitable base (for example an organic base, such as N,N-diethylaniline).

[0248] Compounds of formula (I) may be prepared from compounds of formula (K) by reaction with a suitable source of electropositive Y (reaction scheme 21).

##STR00028##

[0249] For example a compound of formula (I) in which Y is an acyl group may be prepared from a compound of formula (K) by reaction with an acyl halide (for example acetyl chloride) in the presence of a Lewis acid (for example aluminium trichloride) in a suitable solvent (for example nitrobenzene).

[0250] Compounds of formula (H) may also be prepared by reaction of compounds of formula (K) with a suitable source of electrophilic D (reaction scheme 22).

##STR00029##

[0251] For example a compound of formula (H) in which D is a halogen may be prepared from a compound of formula (K) by reaction with an N-halosuccinimide (for example N-chlorosuccinimide) in a suitable solvent (for example dimethylformamide).

[0252] Compounds of formula (K) may be prepared from compounds of formula (L) (shown in reaction scheme 23 below), in which LG represents a leaving group.

##STR00030##

[0253] For example, a compound of formula (K) may be prepared from a compound of formula (L) by reaction with a reagent X--H or X.sup.- in a suitable solvent (for example an ether solvent, such as tetrahydrofuran). The reagent X.sup.- may be generated in situ by addition of a suitable base to X--H, or it may be prepared separately and added as a suitable salt.

[0254] As an additional example a compound of formula (K) may be prepared from a compound of formula (L) by treatment with a reagent X--H in the presence of a suitable catalyst (for example a metal catalyst, such as a palladium source) and optionally a suitable ligand (for example a phosphine ligand, such as Josiphos) in a suitable solvent.

[0255] Compounds of formula (L) may be prepared from compounds of formula (M) (reaction scheme 24 below).

##STR00031##

[0256] For example, a compound of formula (L) in which LG is a halogen atom may be prepared from a compound of formula M by treatment with a suitable reagent (for example a phosphoryl halide such as phosphorous oxychloride) and optionally a suitable base (for example an organic base, such as N,N-diethylaniline).

[0257] Compounds of formula (M) may be prepared from amidines of formula (N) by reaction with a suitable ketoester of formula (O) (reaction scheme 25)

##STR00032##

[0258] For example, a compound of formula (M1), which is a compound of formula (M) in which Z is a carboxylic acid or ester, may be prepared by the reaction of an amidine of formula (N) with an oxaloacetate diester of formula (O1), wherein (O1) is a compound of formula (O) in which Z is CO.sub.2R, optionally in the presence of a suitable base (for example an inorganic base, such as sodium hydroxide), in a suitable solvent (for example water)--reaction scheme 26. The diester (O1) may also be used in the form of a salt, for example the sodium salt.

##STR00033##

[0259] In an additional example, shown schematically below in reaction scheme 27, a compound of formula (M2) (i.e. a compound of formula (M) in which Z is an acetal group) may be prepared by the condensation of an amidine of formula (N) with a ketoester of formula (O2) (i.e. a compound of formula (O) in which Z is CH(OR).sub.2) in the presence of a base (e.g. an alkoxide base, such as sodium methoxide) in a suitable solvent (e.g. an alcohol, such as methanol).

##STR00034##

[0260] In general, amidines (N) and diesters (O) are either well known in the literature or may be prepared using standard methods with which the skilled man is familiar. Thus in a further aspect the invention provides the use of an amidine of formula N as defined above, as an intermediate in the preparation of a herbicide, in particular in the preparation of a compound of formula (I) as defined herein. However, we have found that novel amidines of formula (II) as defined hereinafter, are particularly useful as intermediates for use in the invention. The invention also provides an amidine of formula (II)

##STR00035##

wherein R.sup.7 is methyl, Br, or Cl; R.sup.8 is H, F, Cl, OR.sup.10, or N(R.sup.10).sub.2; R.sup.9 is H, F, or Cl; each R.sup.10 is independently H or C.sub.1-4alkyl, provided that i) R.sup.8 and R.sup.9 are not both hydrogen, (ii) when R.sup.7 is methyl and R.sup.9 is hydrogen, then R.sup.8 is not F, Cl, or NH.sub.2, (iii) when R.sup.7 is Cl and R.sup.8 is hydrogen, R.sup.9 is not Cl, (iv) when R.sup.7 is Cl and R.sup.8 is Cl, R.sup.9 is not hydrogen, and (v) when R.sup.7 is Br, and R9 is hydrogen, R.sup.8 is not F. Particularly preferred compounds of formula (II) are those wherein R.sup.7 is methyl, Br, or Cl; R.sup.8 is F, Cl, OR.sup.10, or N(R.sup.10).sub.2; R.sup.9 is F, or Cl; and each R10 is independently H or C.sub.1-4 alkyl. The skilled man will also appreciate that in many cases amidines of formula (II) may be in salt form, in particular in the form of the HCl salt. Such salts may be obtained routinely by standard methods.

[0261] Compounds of formula (K1) (i.e. compounds of formula K in which X is NH.sub.2) may be prepared by the reaction of amidines of formula (N) with cyanoketones of formula (P) in the presence of a base (e.g. an alkoxide base, such as sodium methoxide) in a suitable solvent (e.g. an alcohol, such as ethanol)--see reaction scheme 28 below.

##STR00036##

[0262] For example a compound of formula (K2), which is a compound of formula (K1) in which Z is CO.sub.2R, may be prepared by the reaction of an amidine of formula (N) with a cyanopyruvate ester of formula (P1) (i.e. a compound of formula (P) in which Z is CO.sub.2R). This is shown schematically in reaction scheme 29 below. In one example the compound of formula (P1) may be reacted first with an alkylating agent (e.g. a methylating agent, such as dimethyl sulphate) in the presence of a base (e.g. an inorganic base, such as sodium bicarbonate) to form an enol ether, which is then reacted with amidine (N) in the presence of a base (e.g. an alkoxide base, such as sodium methoxide).

##STR00037##

[0263] Compounds of formula (P) are known or may be prepared using routine, known methods.

[0264] Compounds of formula (H) may also be prepared from compounds of formula (Q) (shown in reaction scheme 30 below), in which LG represents a leaving group.

##STR00038##

[0265] For example, a compound of formula (H) may be prepared from a compound of formula (Q) by reaction with a reagent X--H or X.sup.- in a suitable solvent (for example an ether solvent, such as tetrahydrofuran, or a polar aprotic solvent, such as dimethylsulphoxide). The reagent X.sup.- may be generated in situ by addition of a suitable base to X--H, or it may be prepared separately and added as a suitable salt.

[0266] As an additional example a compound of formula (H) may be prepared from a compound of formula (Q) by treatment with a reagent X--H in the presence of a suitable catalyst (for example a metal catalyst, such as a palladium source) and optionally a suitable ligand (for example a phosphine ligand, such as Josiphos) in a suitable solvent.

[0267] Compounds of formula (Q) may be prepared from compounds of formula (R) (reaction scheme 31 below).

##STR00039##

[0268] For example, a compound of formula (Q) in which LG is a halogen atom may be prepared from a compound of formula (R) by treatment with a suitable reagent (for example a phosphoryl halide such as phosphorous oxychloride) and optionally a suitable base (for example an organic base, such as N,N-diethylaniline).

[0269] Compounds of formula (R) may be prepared from compounds of formula (M) by reaction with a suitable source of electropositive D (reaction scheme 32 below).

##STR00040##

[0270] For example a compound of formula (R) in which D is a halogen may be prepared from a compound of formula (M) by reaction with an N-halosuccinimide (e.g. N-chlorosuccinimide) in a suitable solvent (e.g. dimethylformamide), or with a metal hypohalite (e.g. sodium hypochlorite) in a suitable solvent (e.g. acidic water).

[0271] Compounds of formula (I) may also be prepared from compounds of formula (S) (see reaction scheme 33), in which LG represents a leaving group (e.g. a halogen or sulphonate).

##STR00041##

[0272] For example, a compound of formula (I) may be prepared from a compound of formula (S) by reaction with a reagent X--H or X.sup.- in a suitable solvent (e.g. methanol, dimethylsulphoxide or water). The reagent X.sup.- may be generated in situ by addition of a suitable base to X--H, or it may be prepared separately and added as a suitable salt.

[0273] As a further example, a compound of formula (I) may be prepared from a compound of formula (S) by treatment with a reagent X--H in the presence of a suitable catalyst (e.g. a metal catalyst, such as a palladium source) and optionally a suitable ligand (e.g. a phosphine ligand, such as Josiphos) in a suitable solvent.

[0274] Compounds of formula (S) may be prepared from compounds of formula (T) (reaction scheme 34).

##STR00042##

[0275] For example, a compound of formula (S) in which LG is a halogen atom may be prepared from a compound of formula (T) by treatment with a suitable reagent (e.g. a phosphoryl halide, such as phosphorous oxychloride) and optionally a suitable base (e.g. an organic base, such as N,N-diethylaniline).

[0276] Compounds of formula (T) may be prepared from amidines of formula (N) by reaction with a suitable ketoester of formula (U) (reaction scheme 35).

##STR00043##

[0277] For example, a compound of formula (T1), which is a compound of formula (T) in which Z is a carboxylic acid or ester, may be prepared by the reaction of an amidine of formula (N) with an oxaloacetate diester of formula (U1) (i.e. a compound of formula (U) in which Z is CO.sub.2R), optionally in the presence of a suitable base (e.g. an inorganic base, such as sodium hydroxide), in a suitable solvent (e.g. water). This is shown schematically below (reaction scheme 36). The diester (U1) may also be used in the form of a salt, for example the sodium salt.

##STR00044##

[0278] Compounds of formula (U) are known in the literature, or may be prepared from compounds of formula (O) by methods well known in the art (reaction scheme 37).

##STR00045##

[0279] Compounds of formula (T) may be prepared by the condensation of amidines of formula (N) with substituted acetate esters of formula (V) and esters of formula (W) in the presence of a base (e.g. an alkoxide base, such as sodium ethoxide), in a suitable solvent (e.g. an alcohol, such as ethanol) (reaction scheme 38).

##STR00046##

[0280] For example a compound of formula (T1) (as defined above) may be prepared by the reaction of an amidine of formula (N) with an acetate ester of formula (V) and a diethyl oxalate of formula (W1) (i.e. a compound of formula (W) in which Z is a carboxylate ester).

[0281] Compounds of formula (V) and (W) are readily available and well known in the literature.

[0282] Alternatively, compounds of formula (T) may be prepared from compounds of formula (M) by reaction with a suitable source of electropositive Y (reaction scheme 39).

##STR00047##

[0283] For example a compound of formula (T) in which Y is an acyl group may be prepared from a compound of formula (M) by reaction with an acyl halide (e.g. acetyl chloride) in the presence of a Lewis acid (e.g. aluminium trichloride) in a suitable solvent (e.g. nitrobenzene).

[0284] Compounds of formula (T) may also be prepared from compounds of formula (R) where D represents a suitable reactive group (reaction scheme 40). Examples of such a reactive group are halogen atoms and sulphonates.

##STR00048##

[0285] For example, such a transformation may be carried out by reaction with a metal or metalloid derivative of the group Y (e.g. a boronic acid or boronate ester) in the presence of a base (e.g. an inorganic base, such as potassium phosphate or caesium fluoride, or an organic base, such as triethylamine), a metal source (e.g. a palladium source such as Pd.sub.2(dba).sub.3) and, optionally, a ligand for the metal (e.g. a phosphine ligand, such as X-Phos) in a suitable solvent (e.g. a single solvent, such as acetonitrile, or a mixed solvent system, such as a mixture of dimethoxyethane and water). The metal catalyst and ligands may also be added as a single, pre-formed, complex (e.g. a palladium/phosphine complex, such as palladium tetrakistriphenylphosphine, bis(triphenylphosphine)palladium dichloride or [1,1'-bis(diphenylphosphino)ferrocene] palladium dichloride).

[0286] Alternatively, compounds of formula (T) may be prepared from compounds of formula (X) (reaction scheme 41 below).

##STR00049##

[0287] For example, a compound of formula (T2), which is a compound of formula (T) in which Z is O--(CHR.sup.w).sub.n--COR.sup.cb (wherein R.sup.w, n and R.sup.cb are as defined hereinbefore), may be prepared from a compound of formula (X) by reaction with a compound of formula (Y) in the presence of a base e.g. sodium hydride, in a suitable solvent e.g. an ether, such as tetrahydrofuran (reaction scheme 42).

##STR00050##

[0288] Compounds of formula (X) may be prepared by the reaction of amidines of formula (N) with malonyl diesters of formula (Z) in the presence of a suitable base (e.g. an inorganic base, such as potassium carbonate, or an alkoxide base, such as sodium methoxide) in a suitable solvent (e.g. an ether, such as diglyme, or an alcohol, such as ethanol) (reaction scheme 43).

##STR00051##

[0289] Diesters of formula (Z) are known in the literature or may be prepared by methods well known in the literature.

[0290] Compounds of formula (X) may be prepared from compounds of formula (AA) by reaction with a suitable source of electropositive Y (reaction scheme 44).

##STR00052##

[0291] For example a compound of formula (X) in which Y is an acyl group may be prepared from a compound of formula (AA) by reaction with an acyl halide e.g. acetyl chloride, in the presence of a Lewis acid e.g. aluminium trichloride, in a suitable solvent e.g. nitrobenzene.

[0292] Alternatively, compounds of formula (X) may be prepared from compounds of formula (AB) where D represents a suitable reactive group (reaction scheme 45). Examples of such a reactive group are halogen atoms and sulphonates.

##STR00053##

[0293] For example, such a transformation may be carried out by reaction with a metal or metalloid derivative of the group Y (e.g. a boronic acid or boronate ester), in the presence of a base (e.g. an inorganic base, such as potassium phosphate or caesium fluoride, or an organic base, such as triethylamine) a metal source (e.g. a palladium source such as Pd.sub.2(dba).sub.3), and, optionally, a ligand for the metal (e.g. a phosphine ligand, such as X-Phos), in a suitable solvent (e.g. a single solvent, such as acetonitrile, or a mixed solvent system, such as a mixture of dimethoxyethane and water). The metal catalyst and ligands may also be added as a single, pre-formed, complex (e.g a palladium/phosphine complex, such as palladium tetrakistriphenylphosphine, bis(triphenylphosphine)palladium dichloride or [1,1'-bis(diphenylphosphino)ferrocene] palladium dichloride).

[0294] Compounds of formula (AB) may be prepared by reaction of compounds of formula (AA) with a suitable source of electropositive D (reaction scheme 46).

##STR00054##

[0295] For example a compound of formula (AB) in which D is a halogen may be prepared from a compound of formula (AA) by reaction with a halogenating agent (e.g. an N-halosuccinimide such as N-chlorosuccinimide, or an elemental halogen such as bromine).

[0296] Compounds of formula (AA) may be prepared from amidines of formula (N) and malonyl diesters of formula (AC) (reaction scheme 47).

##STR00055##

[0297] Diesters of formula (AC) are well known in the literature.

[0298] Compounds of formula (S) may be prepared from compounds of formula (AD) in which B represents a suitable precursor group to LG (reaction scheme 48).

##STR00056##

[0299] For example, a compound of formula (S) in which LG is a sulphone may be prepared from a compound of formula (AD1), which is a compound of formula (AD) in which B is a thioether group, by reaction with a suitable oxidising agent, for example a peracid such as meta-chloroperbenzoic acid) (reaction scheme 49).

##STR00057##

[0300] Compounds of formula (AD) may be prepared from compounds of formula (AE) where D represents a suitable reactive group (reaction scheme 50). Examples of such a reactive group are halogen atoms and sulphonates.

##STR00058##

[0301] For example, such a transformation may be carried out by reaction with a metal or metalloid derivative of the group Y (e.g. a boronic acid or boronate ester) in the presence of a base (e.g. an inorganic base, such as potassium phosphate or caesium fluoride, or an organic base, such as triethylamine), a metal source (e.g. a palladium source such as Pd.sub.2(dba).sub.3) and, optionally, a ligand for the metal (e.g. a phosphine ligand, such as X-Phos) in a suitable solvent (e.g. a single solvent, such as acetonitrile, or a mixed solvent system, such as a mixture of dimethoxyethane and water). The metal catalyst and ligands may also be added as a single, pre-formed, complex (e.g. a palladium/phosphine complex, such as palladium tetrakistriphenylphosphine, bis(triphenylphosphine)palladium dichloride or [1,1'-bis(diphenylphosphino)ferrocene] palladium dichloride).

[0302] Compounds of formula (AE) may be prepared from compounds of formula (Q) by treatment with a reagent B--H or B.sup.-.

[0303] For example, a compound of formula (AE1), which is a compound of formula (AE) in which B is a thioether, may be prepared from a compound of formula (Q) by reaction with a thiol or thiolate anion, optionally in the presence of a suitable base, in a suitable solvent (see reaction scheme 51).

##STR00059##

[0304] Compounds of formula (S) may be prepared from compounds of formula (AF), where LG and LG' (which may be the same or different) are suitable leaving groups, such as halogen atoms or sulphonates (reaction scheme 52).

##STR00060##

[0305] For example a compound of formula (S) in which Z is CO.sub.2R may be prepared from a compound of formula (AF) by reaction with an alcohol ROH and carbon monoxide in the presence of a suitable metal catalyst (e.g. a palladium reagent, such as bis(triphenylphosphine)palladium dichloride) and a suitable base (e.g. an organic base, such as triethylamine). See reaction scheme 53 below. The reaction may conveniently be conducted in an atmosphere of carbon monoxide gas at atmospheric or raised pressure.

##STR00061##

[0306] Alternatively (see reaction scheme 54 below) a compound of formula (S) in which Z is O--(CH.sup.w).sub.n--COR.sup.cb may be prepared from a compound of formula (AF) by reaction with a compound of formula (AG) in the presence of a base (e.g. sodium hydride) in a suitable solvent (e.g. an ether, such as tetrahydrofuran).

##STR00062##

[0307] Compounds of formula (AG) are known compounds or may be prepared from known compounds using methods that are well known in the literature.

[0308] Compounds of formula (AF1), which are compounds of formula (AF) in which LG is the same as LG', may be prepared from compounds of formula (X) by reaction with a suitable reagent, for example a phosphoryl halide or sulphonyl anhydride (reaction scheme 55).

##STR00063##

[0309] For example, a compound of formula (AF1) in which LG and LG' are halogen atoms may be prepared by reaction of a compound of formula (X) with a halogenating agent (e.g. a phosphoryl halide such as phosphorus oxychloride) in the presence of a suitable base (e.g. an organic base, such as N,N-diethylaniline).

[0310] Compounds of formula (I) may be prepared from compounds of formula (AH), where LG is a suitable leaving group, such as a halogen atom or sulphonate (reaction scheme 56).

##STR00064##

[0311] For example a compound of formula (I) in which Z is CO.sub.2R may be prepared from a compound of formula (AH) by reaction with an alcohol ROH and carbon monoxide in the presence of a suitable metal catalyst e.g. a palladium reagent, such as bis(triphenylphosphine)palladium dichloride, and a suitable base e.g. an organic base, such as triethylamine (see reaction scheme 57). The reaction may conveniently be conducted in an atmosphere of carbon monoxide gas at atmospheric or raised pressure.

##STR00065##

[0312] Alternatively a compound of formula (I) in which Z is O--(CHR.sup.w).sub.n--COR.sup.cb (as defined hereinbefore) may be prepared from a compound of formula (AH) by reaction with a compound of formula (AG) in the presence of a base e.g. sodium hydride in a suitable solvent e.g. an ether, such as tetrahydrofuran (reaction scheme 58).

##STR00066##

[0313] Compounds of formula (AH) may be prepared from compounds of formula (AF) (reaction scheme 59).

##STR00067##

[0314] Compounds of formula (I) in which A is a ring may also be prepared from compounds of formula (AI) wherein E represents a suitable cyclisation precursor, by reactions in which ring A is formed (reaction scheme 60). Examples of suitable cyclisation precursors include groups containing carbon-carbon double or triple bonds, such as alkenes and alkynes.

##STR00068##

[0315] For example, a compound of formula (I) in which A is an unsaturated 6-membered ring may be prepared from a compound of formula (AI1) i.e. a compound of formula (AI) in which E is an alkyne, by reaction with a suitable diene (AJ) (reaction scheme 61 below).

##STR00069##

[0316] In a further example, a compound of formula (I) in which A is a cyclopropane may be prepared from a compound of formula (AI2) i.e. a compound of formula (I) in which A is an alkene, by reaction with a suitable cyclopropanation reagent (e.g. a reagent combination that generates a carbene, such as diiodomethane and diethyl zinc) (reaction scheme 62).

##STR00070##

[0317] In an additional example a compound of formula (I) in which A is a 4-membered ring may be prepared from a compound of formula (AI2) by reaction with a suitable reagent (AK) containing a carbon-carbon double bond, for example an alkene.

##STR00071##

[0318] In another example, a compound of formula (I) in which A is a 5-membered ring may be formed from a compound of formula (AI2) by reaction with a suitable 1,3-dipolar species (AL) such as a trimethylenemethane species (reaction scheme 64).

##STR00072##

[0319] As a further example, a compound of formula (I) in which A is an unsaturated 6-membered ring may be prepared from a compound of formula (AI2) by reaction with a suitable diene (AJ) (reaction scheme 65).

##STR00073##

[0320] Compounds of formulae (AJ), (AK) and (AL) are known in the art, or can be made readily using methods that are well known in the literature.

[0321] Compounds of formula (AI1) may be prepared from compounds of formula (A) by a Sonogashira-type reaction with an alkyne (AM) (reaction scheme 66).

##STR00074##

[0322] Compounds of formula (I) in which A is an alkene may be prepared from compounds of formula (AI3), which are compounds of formula (AI) in which E is an aldehyde or ketone group, by olefination reactions that are well known in the literature, for example the Wittig, Peterson, Tebbe and Petasis reactions (see reaction scheme 67, below).

##STR00075##

[0323] Compounds of formula (AI3) may be prepared from compounds of formula (AI2) by oxidative cleavage of the double bond (reaction scheme 68), for example by treatment with ozone.

##STR00076##

[0324] Alternatively compounds of formula (AI3) may be prepared from compounds of formula (AI4), which are compounds of formula (AI) in which E is a 1,2-diol group, by treatment with a suitable oxidising agent, for example sodium periodate (reaction scheme 69).

##STR00077##

[0325] Compounds of formula (AI4) may be prepared from compounds of formula (AI2) by reaction with a suitable dihydroxylation reagent (e.g. an osmium species such as osmium tetroxide) (reaction scheme 70 below).

##STR00078##

[0326] Compounds of formula (I) in which X is NH.sub.2 may be prepared by the condensation of amidines of formula (N) with substituted acetonitriles of formula (AN) and esters of formula (W) (see reaction scheme 71 below). These reactions occur in the presence of a base (e.g. an alkoxide base, such as sodium ethoxide) in a suitable solvent (e.g. an alcohol, such as ethanol).

##STR00079##

[0327] For example, a compound of formula (I) in which Z is CO.sub.2R may be prepared by the reaction of an amidine of formula (N) with a substituted acetonitrile of formula (AN) and an oxalate diester of formula (W1). Compounds of formula (AN) are known in the literature.

[0328] Compounds of formula (I) in which m is 0 and n is 2 may be prepared by the reaction of compounds of formula (AO) with a reagent that can functionalise the double bond (reaction scheme 72).

##STR00080##

[0329] For example, a compound of formula (I) in which R' is hydrogen may be prepared from a compound of formula (AO) by reaction with a suitable reducing agent (e.g. hydrogen gas in the presence of a metal catalyst, such as palladium supported on carbon) (reaction scheme 73).

##STR00081##

[0330] As a further example, a compound of formula (I) in which R' represents vicinal hydroxyl groups may be prepared from a compound of formula (AO) by reaction with a dihydroxylation reagent (e.g. osmium tetroxide) (see reaction scheme 74 below).

##STR00082##

[0331] Compounds of formula (AO) may be prepared by the Heck reaction of compounds of formula (AH) with compounds of formula (AP) in the presence of a suitable metal catalyst (e.g. a palladium species, such as palladium acetate) and a base (e.g. an organic base, such as triethylamine), in a suitable solvent (reaction scheme 75).

##STR00083##

[0332] Compounds of formula (I) may be prepared from different compounds of formula (I) by the conversion of any of the substituents X, Y, Z or A into a different group X, Y, Z or A using techniques that are known in the literature and with which the skilled man will be familiar.

[0333] For example, a compound of formula (I) in which Y is an alkyl group may be prepared from a compound of formula (I) in which Y is an alkenyl or alkynyl group by reduction under suitable conditions (see reaction schemes 76, 77). Examples of such conditions include the use of hydrogen gas in the presence of a suitable catalyst, e.g. a metal catalyst, such as for example, palladium supported on carbon.

##STR00084##

##STR00085##

[0334] A compound of formula (I) in which Y is an alkenyl group may be prepared from a compound of formula (I) in which Y is an alkynyl group by reduction under suitable conditions (reaction scheme 78). Such conditions include reduction using hydrogen gas in the presence of an appropriate metal catalyst, for example a poisoned palladium metal catalyst such as Lindlars catalyst.

##STR00086##

[0335] A compound of formula (I) in which Y is an acyl group may be prepared from a compound of formula (I) in which Y is an enol ether by hydrolysis (reaction scheme 79), for example using an aqueous acid.

##STR00087##

[0336] In an additional example, a compound of formula (I) in which Y is an alkene may be prepared from a compound of formula (I) in which Y is an aldehyde or ketone by using a suitable olefination reaction (reaction scheme 80), for example a Wittig, Horner-Emmons, Peterson or Tebbe reaction.

##STR00088##

[0337] In a further example, a compound of formula (I) in which Y is a cyclopropane may be prepared from a compound of formula (I) in which Y is an alkene by reaction with a suitable cyclopropanation reagent e.g. a reagent combination that generates a carbene, such as diiodomethane and diethyl zinc (reaction scheme 81).

##STR00089##

[0338] A compound of formula (I) in which A is an aromatic or heteroaromatic ring may be prepared from a compound of formula (I) in which A is an alkylthio group (see reaction scheme 82 below).

##STR00090##

[0339] For example, such a transformation may be carried out by reaction with a metal or metalloid derivative of the ring A (for example a boronic acid or boronate ester) in the presence of a metal source (for example, a palladium source such as Pd.sub.2(dba).sub.3) and, optionally, a ligand for the metal (for example a phosphine ligand, such as tri(2-furyl)phosphine), a further metal source (for example a copper complex, such as copper thiophene-2-carboxylate) in a suitable solvent (for example an ether, such as tetrahydrofuran). The metal catalyst and ligands may also be added as a single, pre-formed, complex (for example a palladium/phosphine complex, such as palladium tetrakistriphenylphosphine, bis(triphenylphosphine)palladium dichloride or [1,1'-bis(diphenylphosphino)ferrocene] palladium dichloride).

[0340] In a further example, an unsaturated group A (e.g. an alkene or cycloalkene) may be reduced to form a saturated group (e.g. an alkyl or cycloalkyl group). When A is an unsaturated ring it may be oxidised to form an aromatic ring under standard conditions.

[0341] A compound of formula (I) in which R.sup.5 is not hydrogen may be prepared from a compound of formula (I) in which R.sup.5 is H by reaction with a suitable reagent R.sup.5-LG in which LG is a leaving group such as a halogen atom. Examples of such reagents R.sup.5-LG are alkyl halides and acid anhydrides. For example a compound of formula (I) in which R.sup.5 is COR may be prepared from a compound of formula (I) in which R.sup.5 is H by reaction with an acylating agent such as an acyl chloride in the presence of a base (see reactjon scheme 83 below).

##STR00091##

[0342] Alternatively a compound of formula (I) in which R.sup.5 is not hydrogen may be prepared from a compound of formula (I) in which R.sup.5 is H by reductive amination, involving first a condensation with a carbonyl compound such as an aldehyde or ketone and then reduction of the intermediate imine or iminium ion with a suitable reducing agent such as a metal hydride (e.g. sodium cyanoborohydride).

[0343] In an additional example a compound of formula (I) in which R.sup.cb is OH may be prepared from a compound of formula (I) in which R.sup.cb is OR, by hydrolysis under basic or acidic conditions, for example by treatment with aqueous sodium hydroxide (reaction scheme 84). Alternatively this transformation may be achieved by treatment of the ester with a nucleophile, for example an alkyl thiolate, in a suitable solvent.

##STR00092##

[0344] A compound of formula I in which R.sup.cb is OR may be prepared directly from a compound of formula I in which R.sup.cb is OH by esterification under standard conditions, for example by treatment with an alcohol ROH and an acid catalyst (for example, thionyl chloride). Alternatively, this transformation may be achieved by first preparing an activated derivative of the acid group, for example an acyl halide, followed by reaction with an alcohol.

[0345] Other derivatives of the acid group in compounds of formula (I) in which R.sup.cb is OH may be prepared by standard methods found in the literature. For example a compound of formula (I) in which R.sup.cb is NH.sub.2 may be prepared from a compound of formula (I) in which R.sup.cb is OH by treatment with a suitable coupling reagent (e.g. a carbodiimide, such as dicyclohexylcarbodiimide) and ammonia, optionally with an additive (e.g. dimethylaminopyridine), in a suitable solvent (e.g. dimethylformamide)--see reaction scheme 85. Alternatively, this transformation may be performed by first preparing an activated derivative of the carboxylic acid group (e.g. an acyl halide such as an acid chloride), and then treating the activated derivative with ammonia.

##STR00093##

[0346] One skilled in the art will understand that transformations of this type may equally well be conducted at different stages of the synthetic route, for example converting one compound of formula (T) into a different compound of formula (T).

[0347] The person skilled in the art will also understand that in certain instances more than one transformation can be conducted at a time, utilising the same reaction conditions. For example a compound of formula (I) in which A and Y are the same may be prepared from a compound of formula (i) by reaction with an excess of a metal or metalloid derivative of A, such as a boronic acid, in the presence of a metal catalyst (e.g. a palladium derivative such as Pd.sub.2(dba).sub.3), a ligand (e.g. a phosphine ligand such as X-Phos) and a base (such as, for example, potassium phosphate) in a suitable solvent (reaction scheme 86).

##STR00094##

[0348] Another example is the preparation of a compound of formula (I) in which R.sup.cb is NH.sub.2 from a compound of formula (S1) (i.e. a compound of formula (S) in which R.sup.cb is OR) by treatment with an excess of ammonia in a suitable solvent (see reaction scheme 87 below).

##STR00095##

[0349] A further example is the preparation of a compound of formula (R1) (i.e. a compound of formula (R) in which Z is CO.sub.2R), from a compound of formula (M2) by oxidation using a reagent that also provides a source of electropositive D (for example, N-bromosuccinimide for the case in which D=Br; see reaction scheme 88).

##STR00096##

[0350] The skilled man will appreciate that it is often possible to alter the order in which the transformations above are conducted or to combine them in alternative ways to prepare a wide range of compounds of formula (I).

[0351] One skilled in the art will also realise that some reagents will be incompatible with certain values or combinations of substituents X, Y, Z and A. Accordingly additional steps, such as protection and deprotection steps, will be necessary to achieve the desired transformation, and the skilled man will immediately recognise where this is the case.

[0352] Compounds of formula (I) may be used in unmodified form, i.e. as obtainable from synthesis, but preferably are formulated in any suitable manner using formulation adjuvants, such as carriers, solvents and surface-active substances, for example, as described hereinafter. The invention thus extends to herbicidal compositions and/or formulations comprising a compound of the invention and at least one agriculturally acceptable formulation adjuvant or diluent.

[0353] The formulations can be in various physical forms, e.g. in the form of dusting powders, gels, wettable powders, water-dispersible granules, water-dispersible tablets, effervescent pellets, emulsifiable concentrates, microemulsifiable concentrates, oil-in-water emulsions, oil-flowables, aqueous dispersions, oily dispersions, suspo-emulsions, capsule suspensions, emulsifiable granules, soluble liquids, water-soluble concentrates (with water or a water-miscible organic solvent as carrier), impregnated polymer films or in other forms known e.g. from the Manual on Development and Use of FAO Specifications for Plant Protection Products, 5th Edition, 1999. The formulations can be in the form of concentrates which are diluted prior to use, although ready-to-use formulations can also be made. The dilutions can be made, for example, with water, liquid fertilisers, micronutrients, biological organisms, oil or solvents.

[0354] The formulations can be prepared e.g. by mixing the active ingredient with the formulation adjuvants in order to obtain compositions in the form of finely divided solids, granules, solutions, dispersions or emulsions. The active ingredients can also be formulated with other adjuvants, such as finely divided solids, mineral oils, oils of vegetable or animal origin, modified oils of vegetable or animal origin, organic solvents, water, surface-active substances or combinations thereof. The active ingredients can also be contained in very fine microcapsules consisting of a polymer. Microcapsules usually have a diameter of from 0.1 to 500 microns. Typically, they will contain active ingredients in an amount of about from 25 to 95% by weight of the capsule weight. The active ingredients can be in the form of a monolithic solid, in the form of fine particles in solid or liquid dispersion or in the form of a suitable solution. The encapsulating membranes comprise, for example, natural or synthetic rubbers, cellulose, styrene/butadiene copolymers, polyacrylonitrile, polyacrylate, polyesters, polyamides, polyureas, polyurethane or chemically modified polymers and starch xanthates or other known polymers. Alternatively, very fine microcapsules can be formed in which the active ingredient is contained in the form of finely divided particles in a solid matrix of base substance, but the microcapsules are not themselves encapsulated.

[0355] The formulation adjuvants that are suitable for the preparation of compositions according to the invention are known per se. As liquid carriers there may be used: water, toluene, xylene, petroleum ether, vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, acid anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-trichloroethane, 2-heptanone, alpha-pinene, d-limonene, ethyl lactate, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol, glycerol acetate, glycerol diacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropylbenzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octa-decanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol (PEG), propionic acid, propyl lactate, propylene carbonate, propylene glycol, propylene glycol methyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylenesulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol methyl ether, diethylene glycol methyl ether, methanol, ethanol, isopropanol, and alcohols of higher molecular weight, such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, N-methyl-2-pyrrolidone and the like. Water is generally the carrier of choice for diluting the concentrates. Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed husks, wheat flour, soybean flour, pumice, wood flour, ground walnut shells, lignin and similar substances, as described, for example, in CFR 180.1001. (c) & (d).

[0356] A large number of surface-active substances may advantageously be used in the formulations, especially in those formulations designed to be diluted with a carrier prior to use. Surface-active substances may be anionic, cationic, non-ionic or polymeric and they can be used as emulsifiers, wetting agents or suspending agents or for other purposes. Typical surface-active substances include, for example, salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; salts of alkylarylsulfonates, such as calcium dodecylbenzenesulfonate; alkylphenol/alkylene oxide addition products, such as nonylphenol ethoxylate; alcohol/alkylene oxide addition products, such as tridecylalcohol ethoxylate; soaps, such as sodium stearate; salts of alkylnaphthalenesulfonates, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2-ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryltrimethylammonium chloride, polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono- and di-alkylphosphate esters; and also further substances described e.g. in "McCutcheon's Detergents and Emulsifiers Annual" MC Publishing Corp., Ridgewood N.J., 1981.

[0357] Further adjuvants that can usually be used in pesticidal formulations include crystallisation inhibitors, viscosity modifiers, suspending agents, dyes, anti-oxidants, foaming agents, light absorbers, mixing auxiliaries, antifoams, complexing agents, neutralising or pH-modifying substances and buffers, corrosion inhibitors, fragrances, wetting agents, take-up enhancers, micronutrients, plasticisers, glidants, lubricants, dispersants, thickeners, antifreezes, microbicides, and also liquid and solid fertilisers.

[0358] The compositions according to the invention can additionally include an additive comprising an oil of vegetable or animal origin, a mineral oil, alkyl esters of such oils or mixtures of such oils and oil derivatives. The amount of oil additive in the composition according to the invention is generally from 0.01 to 10%, based on the spray mixture. For example, the oil additive can be added to the spray tank in the desired concentration after the spray mixture has been prepared. Preferred oil additives comprise mineral oils or an oil of vegetable origin, for example rapeseed oil, olive oil or sunflower oil, emulsified vegetable oil, such as AMIGO.RTM. (Rhone-Poulenc Canada Inc.), alkyl esters of oils of vegetable origin, for example the methyl derivatives, or an oil of animal origin, such as fish oil or beef tallow. A preferred additive contains, for example, as active components essentially 80% by weight alkyl esters of fish oils and 15% by weight methylated rapeseed oil, and also 5% by weight of customary emulsifiers and pH modifiers. Especially preferred oil additives comprise alkyl esters of C.sub.8-22 fatty acids, especially the methyl derivatives of C.sub.12-18 fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid, being of importance. Those esters are known as methyl laurate (CAS-111-82-0), methyl palmitate (CAS-112-39-0) and methyl oleate (CAS-112-62-9). A preferred fatty acid methyl ester derivative is Emery.RTM. 2230 and 2231 (Cognis GmbH). Those and other oil derivatives are also known from the Compendium of Herbicide Adjuvants, 5th Edition, Southern Illinois University, 2000. Another preferred adjuvant is Adigor.RTM. (Syngenta AG) which is a methylated rapeseed oil-based adjuvant.

[0359] The application and action of the oil additives can be further improved by combination with surface-active substances, such as non-ionic, anionic or cationic surfactants. Examples of suitable anionic, non-ionic and cationic surfactants are listed on pages 7 and 8 of WO97/34485. Preferred surface-active substances are anionic surfactants of the dodecylbenzylsulfonate type, especially the calcium salts thereof, and also non-ionic surfactants of the fatty alcohol ethoxylate type. Special preference is given to ethoxylated C.sub.12-22 fatty alcohols having a degree of ethoxylation of from 5 to 40. Examples of commercially available surfactants are the Genapol types (Clariant AG). Also preferred are silicone surfactants, especially polyalkyl-oxide-modified heptamethyltriloxanes which are commercially available e.g. as Silwet L-77.RTM., and also perfluorinated surfactants. The concentration of the surface-active substances in relation to the total additive is generally from 1 to 30% by weight. Examples of oil additives consisting of mixtures of oil or mineral oils or derivatives thereof with surfactants are Edenor ME SU.RTM., Turbocharge.RTM. (Syngenta AG, CH) or ActipronC (BP Oil UK Limited, GB).

[0360] If desired, it is also possible for the mentioned surface-active substances to be used in the formulations on their own, that is to say without oil additives.

[0361] Furthermore, the addition of an organic solvent to the oil additive/surfactant mixture may contribute to an additional enhancement of action. Suitable solvents are, for example, Solvesso.RTM. (ESSO) or Aromatic Solvent.RTM. (Exxon Corporation). The concentration of such solvents can be from 10 to 80% by weight of the total weight. Oil additives that are present in admixture with solvents are described, for example, in U.S. Pat. No. 4,834,908. A commercially available oil additive disclosed therein is known by the name MERGE.RTM. (BASF Corporation). A further oil additive that is preferred according to the invention is SCORE.RTM. (Syngenta Crop Protection Canada).

[0362] In addition to the oil additives listed above, for the purpose of enhancing the action of the compositions according to the invention it is also possible for formulations of alkylpyrrolidones (e.g. Agrimax.RTM.) to be added to the spray mixture. Formulations of synthetic lattices, e.g. polyacrylamide, polyvinyl compounds or poly-1-p-menthene (e.g. Bond.RTM., Courier.RTM. or Emerald.RTM.) may also be used. It is also possible for solutions that contain propionic acid, for example Eurogkem Pen-e-trate.RTM., to be added to the spray mixture as action-enhancing agent.

[0363] Herbicidal compositions of the invention generally comprise from 0.1 to 99% by weight, especially from 0.1 to 95% by weight, compounds of formula (I) and from 1 to 99.9% by weight of a formulation adjuvant which preferably includes from 0 to 25% by weight of a surface-active substance. Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ dilute formulations.

[0364] Examples of preferred formulation types and their typical compositions are given below (% is percent by weight). Wettable powders as described herein are one particularly preferred type of formulation for use in the invention. In other preferred embodiments, in particular where the compound/composition/formulation of the invention is intended for use on turf, granular (inert or fertiliser) formulations as described herein are particularly suitable.

Emulsifiable Concentrates:

[0365] active ingredient: 1 to 95%, preferably 60 to 90% surface-active agent: 1 to 30%, preferably 5 to 20% liquid carrier: 1 to 80%, preferably 1 to 35%

Dusts:

[0366] active ingredient: 0.1 to 10%, preferably 0.1 to 5% solid carrier: 99.9 to 90%, preferably 99.9 to 99%

Suspension Concentrates:

[0367] active ingredient: 5 to 75%, preferably 10 to 50% water: 94 to 24%, preferably 88 to 30% surface-active agent: 1 to 40%, preferably 2 to 30%

Wettable Powders:

[0368] active ingredient: 0.5 to 90%, preferably 1 to 80% surface-active agent: 0.5 to 20%, preferably 1 to 15% solid carrier: 5 to 95%, preferably 15 to 90%

Granules:

[0369] active ingredient: 0.1 to 30%, preferably 0.1 to 15% solid carrier: 99.5 to 70%, preferably 97 to 85% The following Examples further illustrate, but do not limit, the invention.

Formulation Examples for Herbicides of Formula (I) (%=% by Weight)

TABLE-US-00002 [0370] F1. Emulsifiable concentrates a) b) c) d) active ingredient 5% 10% 25% 50% calcium dodecylbenzenesulfonate 6% 8% 6% 8% castor oil polyglycol ether 4% -- 4% 4% (36 mol of ethylene oxide) octylphenol polyglycol ether -- 4% -- 2% (7-8 mol of ethylene oxide) NMP -- -- 10% 20% arom. hydrocarbon mixture 85% 78% 55% 16% (C.sub.9-C.sub.12)

[0371] Emulsions of any desired concentration can be obtained from such concentrates by dilution with water.

TABLE-US-00003 F2. Solutions a) b) c) d) active ingredient 5% 10% 50% 90% 1-methoxy-3-(3-methoxy- -- 20% 20% -- propoxy)-propane polyethylene glycol 20% 10% -- -- MW 400 NMP -- -- 30% 10% arom. hydrocarbon mixture 75% 60% -- -- (C.sub.9-C.sub.12)

[0372] The solutions are suitable for use in the form of microdrops.

TABLE-US-00004 F3. Wettable powders a) b) c) d) active ingredient 5% 25% 50% 80% sodium lignosulfonate 4% -- 3% -- sodium lauryl sulphate 2% 3% -- 4% sodium -- 6% 5% 6% diisobutylnaphthalene- sulfonate octylphenol polyglycol -- 1% 2% -- ether (7-8 mol of ethylene oxide) highly dispersed silicic acid 1% 3% 5% 10% kaolin 88% 62% 35% --

[0373] The active ingredient is mixed thoroughly with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders which can be diluted with water to give suspensions of any desired concentration.

TABLE-US-00005 F4. Coated granules a) b) c) active ingredient 0.1% 5% 15% highly dispersed silicic acid 0.9% 2% 2% inorganic carrier 99.0% 93% 83% (diameter 0.1-1 mm) e.g. CaCO.sub.3 or SiO.sub.2

[0374] The active ingredient is dissolved in methylene chloride and applied to the carrier by spraying, and the solvent is then evaporated off in vacuo.

TABLE-US-00006 F5. Coated granules a) b) c) active ingredient 0.1% 5% 15% polyethylene glycol MW 200 1.0% 2% 3% highly dispersed silicic acid 0.9% 1% 2% inorganic carrier 98.0% 92% 80% (diameter 0.1-1 mm) e.g. CaCO.sub.3 or SiO.sub.2

[0375] The finely ground active ingredient is uniformly applied, in a mixer, to the carrier moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.

TABLE-US-00007 F6. Extruder granules a) b) c) d) active ingredient 0.1% 3% 5% 15% sodium lignosulfonate 1.5% 2% 3% 4% carboxymethylcellulose 1.4% 2% 2% 2% kaolin 97.0% 93% 90% 79%

[0376] The active ingredient is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.

TABLE-US-00008 F7. Dusts a) b) c) active ingredient 0.1% 1% 5% talcum 39.9% 49% 35% kaolin 60.0% 50% 60%

[0377] Ready-to-use dusts are obtained by mixing the active ingredient with the carriers and grinding the mixture in a suitable mill.

TABLE-US-00009 F8. Suspension concentrates a) b) c) d) active ingredient 3% 10% 25% 50% ethylene glycol 5% 5% 5% 5% nonylphenol polyglycol -- 1% 2% -- ether (15 mol of ethylene oxide) sodium lignosulfonate 3% 3% 4% 5% carboxymethylcellulose 1% 1% 1% 1% 37% aqueous formaldehyde 0.2% 0.2% 0.2% 0.2% solution silicone oil emulsion 0.8% 0.8% 0.8% 0.8% water 87% 79% 62% 38%

[0378] The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired concentration can be obtained by dilution with water.

[0379] Compounds of the invention (as well as mixtures and/or compositions or formulations containing the same) find utility as herbicides, and may thus be employed in methods of controlling plant growth. Such methods involve applying to the plants or to the locus thereof an herbicidally effective amount of said compound, or composition comprising the same (or mixture as described hereinafter). The invention thus also relates to a method of inhibiting plant growth which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (I), composition, or mixture of the invention. In particular the invention provides a method of controlling weeds in crops of useful plants, which comprising applying to said weeds or the locus of said weeds, or to said crop of useful plants, a compound of formula I or a composition or mixture containing the same.

[0380] The term "locus" as used herein includes not only areas where weeds may already be growing, but also areas where weeds have yet to emerge, and also to areas under cultivation with respect to crops of useful plants. Areas under cultivation include land on which the crop plants are already growing and land intended for cultivation with such crop plants.

[0381] A compound, composition, and/or mixture of the invention may be used in a pre-emergence application and/or in a post-emergence application in order to mediate its effect.

[0382] Crops of useful plants in which compounds of formula (I), as well as formulations and/or mixtures containing the same, may be used according to the invention include perennial crops, such as citrus fruit, grapevines, nuts, oil palms, olives, pome fruit, stone fruit and rubber, and annual arable crops, such as cereals, for example barley and wheat, cotton, oilseed rape, maize, rice, soy beans, sugar beet, sugar cane, sunflowers, ornamentals and vegetables, especially cereals and maize.

[0383] Compounds of formula (I), formulations and/or mixtures containing the same may also be used on turf, pasture, rangeland, rights of way etc. In particular they may used on golf-courses, lawns, parks, sports-fields, race-courses and the like.

[0384] Crops are to be understood as also including those crops which have been rendered tolerant to herbicides or classes of herbicides (e.g. ALS-, GS-, EPSPS-, PPO- and HPPD-inhibitors and synthetic auxins) by conventional methods of breeding or by genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding is Clearfield.RTM. summer rape (canola). Examples of crops that have been rendered tolerant to herbicides by genetic engineering methods include e.g. glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady.RTM. and LibertyLink.RTM., as well as corn, soybean and cotton that have been engineered to be resistant to Dicamba, phenoxypropionic acids, pyridyloxyacetic acids and/or picolinate auxins.

[0385] Crops are also to be understood as being those which have been rendered resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to European corn borer), Bt cotton (resistant to cotton boll weevil) and also Bt potatoes (resistant to Colorado beetle). Examples of Bt maize are the Bt 176 maize hybrids of NK.RTM. (Syngenta Seeds). The Bt toxin is a protein that is formed naturally by Bacillus thuringiensis soil bacteria. Examples of toxins, or transgenic plants able to synthesise such toxins, are described in EP-A-451 878, EP-A-374 753, WO 93/07278, WO 95/34656, WO 03/052073 and EP-A-427 529. Examples of transgenic plants comprising one or more genes that code for an insecticidal resistance and express one or more toxins are KnockOut.RTM. (maize), Yield Gard.RTM. (maize), NuCOTIN33B.RTM. (cotton), Bollgard.RTM. (cotton), NewLeaf.RTM. (potatoes), NatureGard.RTM. and Protexcta.RTM.. Plant crops or seed material thereof can be both resistant to herbicides and, at the same time, resistant to insect feeding ("stacked" transgenic events). For example, seed can have the ability to express an insecticidal Cry3 protein while at the same time being tolerant to glyphosate.

[0386] Crops are also to be understood as being those which are obtained by conventional methods of breeding or genetic engineering and contain so-called output traits (e.g. improved storage stability, higher nutritional value and improved flavour).

[0387] The term "weeds" as used herein means any undesired plant, and thus includes not only agronomically important weeds as described below, but also volunteer crop plants.

[0388] Compounds of formula (I) may be used against a large number of agronomically important weeds. The weeds that may be controlled include both monocotyledonous and dicotyledonous weeds, such as, for example, Alisma spp, Leptochloa chinensis, Stellaria, Nasturtium, Agrostis, Digitaria, Avena, Setaria, Sinapis, Lolium, Solanum, Echinochloa, Scirpus, Monochoria, Sagittaria, Bromus, Alopecurus, Sorghum, Rottboellia, Cyperus, Abutilon, Sida, Xanthium, Amaranthus, Ambrosia, Brachiaria, Bidens, Chenopodium, Ipomoea, Chrysanthemum, Galium, Viola, Veronica, and Ischaemum spp.

[0389] The rates of application of compounds of formula (I) may vary within wide limits and depend on the nature of the soil, the method of application (pre- or post-emergence; seed dressing; application to the seed furrow; no tillage application etc.), the crop plant, or weed to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop. The compounds of formula I according to the invention are generally applied at a rate of from 10 to 2000 g/ha, especially from 50 to 1000 g/ha.

[0390] Any method of application to weeds/crop of useful plant, or locus thereof, which is routinely used in agriculture may be used, for example application by spray or broadcast method typically after suitable dilution of a compound of formula (I) (whether said compound is formulated and/or in combination with one or more further active ingredients and/or safeners, as described herein).

[0391] The compounds of formula (I) according to the invention can also be used in combination with other active ingredients, e.g. other herbicides, and/or insecticides, and/or acaricides, and/or nematocides, and/or molluscicides, and/or fungicides, and/or plant growth regulators. Such mixtures, and the use of such mixtures to control weeds and/or undesired plant growth form yet further aspects of the invention. For the avoidance of doubt, mixtures of invention also include mixtures of two or more different compounds of formula (I).

Where a compound of formula (I) is combined with at least one additional herbicide, the following mixtures of the compound of formula (I) are particularly preferred. Compound of formula (I)+acetochlor, compound of formula (I)+acifluorfen, compound of formula (I)+acifluorfen-sodium, compound of formula (I)+aclonifen, compound of formula (I)+acrolein, compound of formula (I)+alachlor, compound of formula (I)+alloxydim, compound of formula (I)+allyl alcohol, compound of formula (I)+ametryn, compound of formula (I)+amicarbazone, compound of formula (I)+amidosulfuron, compound of formula (I)+aminopyralid, compound of formula (I)+aminocyclopyrachlor, compound of formula (I)+amitrole, compound of formula (I)+ammonium sulfamate, compound of formula (I)+anilofos, compound of formula (I)+asulam, compound of formula (I)+atrazine, formula (I)+aviglycine, formula (I)+azafenidin, compound of formula (I)+azimsulfuron, compound of formula (I)+BCPC, compound of formula (I)+beflubutamid, compound of formula (I)+benazolin, formula (I)+bencarbazone, compound of formula (I)+benfluralin, compound of formula (I)+benfuresate, compound of formula (I)+bensulfuron, compound of formula (I)+bensulfuron-methyl, compound of formula (I)+bensulide, compound of formula (I)+bentazone, compound of formula (I)+benzfendizone, compound of formula (I)+benzobicyclon, compound of formula (I)+benzofenap, compound of formula (I)+bifenox, compound of formula (I)+bilanafos, compound of formula (I)+bispyribac, compound of formula (I)+bispyribac-sodium, compound of formula (I)+borax, compound of formula (I)+bromacil, compound of formula (I)+bromobutide, formula (I)+bromophenoxim, compound of formula (I)+bromoxynil, compound of formula (I)+butachlor, compound of formula (I)+butafenacil, compound of formula (I)+butamifos, compound of formula (I)+butralin, compound of formula (I)+butroxydim, compound of formula (I)+butylate, compound of formula (I)+cacodylic acid, compound of formula (I)+calcium chlorate, compound of formula (I)+cafenstrole, compound of formula (I)+carbetamide, compound of formula (I)+carfentrazone, compound of formula (I)+carfentrazone-ethyl, compound of formula (I)+CDEA, compound of formula (I)+CEPC, compound of formula (I)+chlorflurenol, compound of formula (I)+chlorflurenol-methyl, compound of formula (I)+chloridazon, compound of formula (I)+chlorimuron, compound of formula (I)+chlorimuron-ethyl, compound of formula (I)+chloroacetic acid, compound of formula (I)+chlorotoluron, compound of formula (I)+chlorpropham, compound of formula (I)+chlorsulfuron, compound of formula (I)+chlorthal, compound of formula (I)+chlorthal-dimethyl, compound of formula (I)+cinidon-ethyl, compound of formula (I)+cinmethylin, compound of formula (I)+cinosulfuron, compound of formula (I)+cisanilide, compound of formula (I)+clethodim, compound of formula (I)+clodinafop, compound of formula (I)+clodinafop-propargyl, compound of formula (I)+clomazone, compound of formula (I)+clomeprop, compound of formula (I)+clopyralid, compound of formula (I)+cloransulam, compound of formula (I)+cloransulam-methyl, compound of formula (I)+CMA, compound of formula (I)+4-CPB, compound of formula (I)+CPMF, compound of formula (I)+4-CPP, compound of formula (I)+CPPC, compound of formula (I)+cresol, compound of formula (I)+cumyluron, compound of formula (I)+cyanamide, compound of formula (I)+cyanazine, compound of formula (I)+cycloate, compound of formula (I)+cyclosulfamuron, compound of formula (I)+cycloxydim, compound of formula (I)+cyhalofop, compound of formula (I)+cyhalofop-butyl, compound of formula (I)+2,4-D, compound of formula (I)+3,4-DA, compound of formula (I)+daimuron, compound of formula (I)+dalapon, compound of formula (I)+dazomet, compound of formula (I)+2,4-DB, compound of formula (I)+3,4-DB, compound of formula (I)+2,4-DEB, compound of formula (I)+desmedipham, formula (I)+desmetryn, compound of formula (I)+dicamba, compound of formula (I)+dichlobenil, compound of formula (I)+ortho-dichlorobenzene, compound of formula (I)+para-dichlorobenzene, compound of formula (I)+dichlorprop, compound of formula (I)+dichlorprop-P, compound of formula (I)+diclofop, compound of formula (I)+diclofop-methyl, compound of formula (I)+diclosulam, compound of formula (I)+difenzoquat, compound of formula (I)+difenzoquat metilsulfate, compound of formula (I)+diflufenican, compound of formula (I)+diflufenzopyr, compound of formula (I)+dimefuron, compound of formula (I)+dimepiperate, compound of formula (I)+dimethachlor, compound of formula (I)+dimethametryn, compound of formula (I)+dimethenamid, compound of formula (I)+dimethenamid-P, compound of formula (I)+dimethipin, compound of formula (I)+dimethylarsinic acid, compound of formula (I)+dinitramine, compound of formula (I)+dinoterb, compound of formula (I)+diphenamid, formula (I)+dipropetryn, compound of formula (I)+diquat, compound of formula (I)+diquat dibromide, compound of formula (I)+dithiopyr, compound of formula (I)+diuron, compound of formula (I)+DNOC, compound of formula (I)+3,4-DP, compound of formula (I)+DSMA, compound of formula (I)+EBEP, compound of formula (I)+endothal, compound of formula (I)+EPTC, compound of formula (I)+esprocarb, compound of formula (I)+ethalfluralin, compound of formula (I)+ethametsulfuron, compound of formula (I)+ethametsulfuron-methyl, formula (I)+ethephon, compound of formula (I)+ethofumesate, compound of formula (I)+ethoxyfen, compound of formula (I)+ethoxysulfuron, compound of formula (I)+etobenzanid, compound of formula (I)+fenoxaprop, compound of formula (I)+fenoxaprop-P, compound of formula (I)+fenoxaprop-ethyl, compound of formula (I)+fenoxaprop-P-ethyl, compound of formula (I)+fentrazamide, compound of formula (I)+ferrous sulfate, compound of formula (I)+flamprop-M, compound of formula (I)+flazasulfuron, compound of formula (I)+florasulam, compound of formula (I)+fluazifop, compound of formula (I)+fluazifop-butyl, compound of formula (I)+fluazifop-P, compound of formula (I)+fluazifop-P-butyl, formula (I)+fluazolate, compound of formula (I)+flucarbazone, compound of formula (I)+flucarbazone-sodium, compound of formula (I)+flucetosulfuron, compound of formula (I)+fluchloralin, compound of formula (I)+flufenacet, compound of formula (I)+flufenpyr, compound of formula (I)+flufenpyr-ethyl, formula (I)+flumetralin, compound of formula (I)+flumetsulam, compound of formula (I)+flumiclorac, compound of formula (I)+flumiclorac-pentyl, compound of formula (I)+flumioxazin, formula (I)+flumipropin, compound of formula (I)+fluometuron, compound of formula (I)+fluoroglycofen, compound of formula (I)+fluoroglycofen-ethyl, formula (I)+fluoxaprop, formula (I)+flupoxam, formula (I)+flupropacil, compound of formula (I)+flupropanate, compound of formula (I)+flupyrsulfuron, compound of formula (I)+flupyrsulfuron-methyl-sodium, compound of formula (I)+flurenol, compound of formula (I)+fluridone, compound of formula (I)+fluorochloridone, compound of formula (I)+fluoroxypyr, compound of formula (I)+flurtamone, compound of formula (I)+fluthiacet, compound of formula (I)+fluthiacet-methyl, compound of formula (I)+fomesafen, compound of formula (I)+foramsulfuron, compound of formula (I)+fosamine, compound of formula (I)+glufosinate, compound of formula (I)+glufosinate-ammonium, compound of formula (I)+glyphosate, compound of formula (I)+halosulfuron, compound of formula (I)+halosulfuron-methyl, compound of formula (I)+haloxyfop, compound of formula (I)+haloxyfop-P, compound of formula (I)+HC-252, compound of formula (I)+hexazinone, compound of formula (I)+imazamethabenz, compound of formula (I)+imazamethabenz-methyl, compound of formula (I)+imazamox, compound of formula (I)+imazapic, compound of formula (I)+imazapyr, compound of formula (I)+imazaquin, compound of formula (I)+imazethapyr, compound of formula (I)+imazosulfuron, compound of formula (I)+indanofan, compound of formula (I)+iodomethane, compound of formula (I)+iodosulfuron, compound of formula (I)+iodosulfuron-methyl-sodium, compound of formula (I)+ioxynil, compound of formula (I)+isoproturon, compound of formula (I)+isouron, compound of formula (I)+isoxaben, compound of formula (I)+isoxachlortole, compound of formula (I)+isoxaflutole, formula (I)+isoxapyrifop, compound of formula (I)+karbutilate, compound of formula (I)+lactofen, compound of formula (I)+lenacil, compound of formula (I)+linuron, compound of formula (I)+MAA, compound of formula (I)+MAMA, compound of formula (I)+MCPA, compound of formula (I)+MCPA-thioethyl, compound of formula (I)+MCPB, compound of formula (I)+mecoprop, compound of formula (I)+mecoprop-P, compound of formula (I)+mefenacet, compound of formula (I)+mefluidide, compound of formula (I)+mesosulfuron, compound of formula (I)+mesosulfuron-methyl, compound of formula (I)+mesotrione, compound of formula (I)+metam, compound of formula (I)+metamifop, compound of formula (I)+metamitron, compound of formula (I)+metazachlor, compound of formula (I)+methabenzthiazuron, formula (I)+methazole, compound of formula (I)+methylarsonic acid, compound of formula (I)+methyldymron, compound of formula (I)+methyl isothiocyanate, compound of formula (I)+metobenzuron, formula (I)+metobromuron, compound of formula (I)+metolachlor, compound of formula (I)+S-metolachlor, compound of formula (I)+metosulam, compound of formula (I)+metoxuron, compound of formula (I)+metribuzin, compound of formula (I)+metsulfuron, compound of formula (I)+metsulfuron-methyl, compound of formula (I)+MK-616, compound of formula (I)+molinate, compound of formula (I)+monolinuron, compound of formula (I)+MSMA, compound of formula (I)+naproanilide, compound of formula (I)+napropamide, compound of formula (I)+naptalam, formula (I)+NDA-402989, compound of formula (I)+neburon, compound of formula (I)+nicosulfuron, formula (I)+nipyraclofen, formula (I)+n-methyl glyphosate, compound of formula (I)+nonanoic acid, compound of formula (I)+norflurazon, compound of formula (I)+oleic acid (fatty acids), compound of formula (I)+orbencarb, compound of formula (I)+orthosulfamuron, compound of formula (I)+oryzalin, compound of formula (I)+oxadiargyl, compound of formula (I)+oxadiazon, compound of formula (I)+oxasulfuron, compound of formula (I)+oxaziclomefone, compound of formula (I)+oxyfluorfen, compound of formula (I)+paraquat, compound of formula (I)+paraquat dichloride, compound of formula (I)+pebulate, compound of formula (I)+pendimethalin, compound of formula (I)+penoxsulam, compound of formula (I)+pentachlorophenol, compound of formula (I)+pentanochlor, compound of formula (I)+pentoxazone, compound of formula (I)+pethoxamid, compound of formula (I)+petrolium oils, compound of formula (I)+phenmedipham, compound of formula (I)+phenmedipham-ethyl, compound of formula (I)+picloram, compound of formula (I)+picolinafen, compound of formula (I)+pinoxaden, compound of formula (I)+piperophos, compound of formula (I)+potassium arsenite, compound of formula (I)+potassium azide, compound of formula (I)+pretilachlor, compound of formula (I)+primisulfuron, compound of formula (I)+primisulfuron-methyl, compound of formula (I)+prodiamine, compound of formula (I)+profluazol, compound of formula (I)+profoxydim, formula (I)+prohexadione-calcium, compound of formula (I)+prometon, compound of formula (I)+prometryn, compound of formula (I)+propachlor, compound of formula (I)+propanil, compound of formula (I)+propaquizafop, compound of formula (I)+propazine, compound of formula (I)+propham, compound of formula (I)+propisochlor, compound of formula (I)+propoxycarbazone, compound of formula (I)+propoxycarbazone-sodium, compound of formula (I)+propyzamide, compound of formula (I)+prosulfocarb, compound of formula (I)+prosulfuron, compound of formula (I)+pyraclonil, compound of formula (I)+pyraflufen, compound of formula (I)+pyraflufen-ethyl, formula (I)+pyrasulfotole, compound of formula (I)+pyrazolynate, compound of formula (I)+pyrazosulfuron, compound of formula (I)+pyrazosulfuron-ethyl, compound of formula (I)+pyrazoxyfen, compound of formula (I)+pyribenzoxim, compound of formula (I)+pyributicarb, compound of formula (I)+pyridafol, compound of formula (I)+pyridate, compound of formula (I)+pyriftalid, compound of formula (I)+pyriminobac, compound of formula (I)+pyriminobac-methyl, compound of formula (I)+pyrimisulfan, compound of formula (I)+pyrithiobac, compound of formula (I)+pyrithiobac-sodium, formula (I)+pyroxasulfone, formula (I)+pyroxulam, compound of formula (I)+quinclorac, compound of formula (I)+quinmerac, compound of formula (I)+quinoclamine, compound of formula (I)+quizalofop, compound of formula (I)+quizalofop-P, compound of formula (I)+quizalofop-ethyl, compound of formula (I)+quizalofop-P-ethyl, compound of formula (I)+rimsulfuron, compound of formula (I)+sethoxydim, compound of formula (I)+siduron, compound of formula (I)+simazine, compound of formula (I)+simetryn, compound of formula (I)+SMA, compound of formula (I)+sodium arsenite, compound of formula (I)+sodium azide, compound of formula (I)+sodium chlorate, compound of formula (I)+sulcotrione, compound of formula (I)+sulfentrazone, compound of formula (I)+sulfometuron, compound of formula (I)+sulfometuron-methyl, compound of formula (I)+sulfosate, compound of formula (I)+sulfosulfuron, compound of formula (I)+sulfuric acid, compound of formula (I)+tar oils, compound of formula (I)+2,3,6-TBA, compound of formula (I)+TCA, compound of formula (I)+TCA-sodium, formula (I)+tebutam, compound of formula (I)+tebuthiuron, formula (I)+tefuryltrione, compound of formula 1+tembotrione, compound of formula (I)+tepraloxydim, compound of formula (I)+terbacil, compound of formula (I)+terbumeton, compound of formula (I)+terbuthylazine, compound of formula (I)+terbutryn, compound of formula (I)+thenylchlor, compound of formula (I)+thiazafluoron, compound of formula (I)+thiazopyr, compound of formula (I)+thifensulfuron, compound of formula (I)+thiencarbazone, compound of formula (I)+thifensulfuron-methyl, compound of formula (I)+thiobencarb, compound of formula (I)+tiocarbazil, compound of formula (I)+topramezone, compound of formula (I)+tralkoxydim, compound of formula (I)+tri-allate, compound of formula (I)+triasulfuron, compound of formula (I)+triaziflam, compound of formula (I)+tribenuron, compound of formula (I)+tribenuron-methyl, compound of formula (I)+tricamba, compound of formula (I)+triclopyr, compound of formula (I)+trietazine, compound of formula (I)+trifloxysulfuron, compound of formula (I)+trifloxysulfuron-sodium, compound of formula (I)+trifluralin, compound of formula (I)+triflusulfuron, compound of formula (I)+triflusulfuron-methyl, compound of formula (I)+trifop, compound of formula (I)+trifop-methyl, compound of formula (I)+trihydroxytriazine, compound of formula (I)+trinexapac-ethyl, compound of formula (I)+tritosulfuron, compound of formula (I)+[3-[2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4-dioxo-1,2,3,4- -tetrahydropyrimidin-3-yl)phenoxy]-2-pyridyloxy]acetic acid ethyl ester (CAS RN 353292-31-6), compound of formula (I)+4-hydroxy-3-[[2-[(2-methoxyethoxy)methyl]-6-(trifluoromethyl)-3-pyrid- inyl]carbonyl]-bicyclo[3.2.1]oct-3-en-2-one (CAS RN 352010-68-5), and compound of formula (I)+4-hydroxy-3-[[2-(3-methoxypropyl)-6-(difluoromethyl)-3-pyridinyl]carb- onyl]-bicyclo[3.2.1]oct-3-en-2-one.

[0393] Whilst two-way mixtures of a compound of formula (I) and another herbicide are explicitly disclosed above, the skilled man will appreciate that the invention extends to three-way, and further multiple combinations comprising the above two-way mixtures.

[0394] In preferred embodiments a compound of formula (I) is combined with an acetolactate synthase inhibitor, (e.g. one or more of florasulam, metsulfuron, thifensulfuron, tribenuron, triasulfuron, flucarbazone, flupyrsulfuron, iodosulfuron, mesosulfuron, propoxicarbazone, sulfosulfuron, pyroxsulam and tritosulfuron, as well as salts or esters thereof), a synthetic auxin herbicide (e.g. one or more of aminocyclopyrachlor, aminopyralid, clopyralid, 2,4-D, 2,4-DB, dicamba, dichlorprop, fluoroxypyr, MCPA, MCPB, mecopropand mecoprop-P), an ACCase-inhibiting herbicide (e.g. one or more of phenylpyrazolin; pinoxaden; an aryloxyphenoxypropionic herbicide such as clodinafop, cyhalofop, diclofop, fenoxaprop, fluazifop, haloxyfop, quizalofop, trifop and mixtures thereof, as well as the isomers thereof, for example, fenoxaprop-P, fluazifop-P, haloxyfop-P, quizalofop-P; and a cyclohexanedione herbicide such as alloxydim; butroxydim, clethodim, cycloxydim, profoxydim, sethoxydim, tepraloxydim and tralkoxydim, as well as salts or esters thereof), and/or an auxin transport inhibitor such as semicarbazone (e.g. diflufenzopyr, in particular the sodium salt) or phthalamate compound (e.g. naptalam).

[0395] Particularly preferred mixture partners for compounds of formula (I) are: florasulam, iodosulfuron-methyl-sodium, mesosulfuron-methyl, metsulfuron-methyl, thifensulfuron, triasulfuron, tribenuron-methyl or pyroxsulam; dicamba, fluoroxypyr, MCPA, mecoprop or mecoprop-P; clodinafop-propargyl, cyhalofop-butyl, diclofop-methyl, fenoxaprop-ethyl, fenoxaprop-P-ethyl, fluazifop-butyl, fluazifop-P-butyl, haloxyfop-methyl, haloxyfop-P-methyl, pinoxaden, propaquizafop, quizalofop-ethyl, quizalofop-P-ethyl, tralkoxydim, trifop-methyl, diflufenzopyr-Na, and naptalam.

[0396] For the avoidance of doubt, even if not explicitly stated above, the mixing partners of the compound of formula (I) may also be in the form of any suitable agrochemically acceptable ester or salt, as mentioned e.g. in The Pesticide Manual, Thirteenth Edition, British Crop Protection Council, 2003.

[0397] The mixing ratio of the compound of formula (I) to the mixing partner is preferably from 1:100 to 1000:1.

[0398] The mixtures can advantageously be used in the above-mentioned formulations (in which case "active ingredient" relates to the respective mixture of compound of formula (I) with the mixing partner).

[0399] The compounds of formula (I) according to the invention can also be used in combination with one or more safeners. Likewise, mixtures of a compound of formula (I) according to the invention with one or more further active ingredients, in particular with one or more further herbicides, can also be used in combination with one or more safeners. Suitable safeners for use in combination with compounds of formula (I) include AD 67 (MON 4660), benoxacor, cloquintocet-mexyl, cyometrinil and the corresponding (Z) isomer, cyprosulfamide (CAS RN 221667-31-8), dichlormid, fenchlorazole-ethyl, fenclorim, flurazole, fluxofenim, furilazole and the corresponding R isomer, isoxadifen-ethyl, mefenpyr-diethyl, oxabetrinil, naphthalic anhydride (CAS RN 81-84-5) and N-isopropyl-4-(2-methoxy-benzoylsulfamoyl)-benzamide (CAS RN 221668-34-4). Particularly preferred safeners for use in the invention are cloquintocet-mexyl, cyprosulfamide, fenchlorazole-ethyl and mefenpyr-diethyl. The safeners of the compound of formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 13.sup.th Edition supra. The reference to cloquintocet-mexyl also applies to a lithium, sodium, potassium, calcium, magnesium, aluminium, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salt thereof as disclosed in WO02/34048, and the reference to fenchlorazole-ethyl also applies to fenchlorazole, etc.

[0400] Preferably the mixing ratio of compound of formula (I) to safener is from 100:1 to 1:10, especially from 20:1 to 1:1.

[0401] The mixtures can advantageously be used in the above-mentioned formulations (in which case "active ingredient" relates to the respective mixture of compound of formula (I) with the safener).

[0402] Preferred mixtures of a compound of formula (I) with further herbicides and safeners include: a compound of formula (I)+pinoxaden+cloquinctocet-mexyl, a compound of formula (I)+clodinafop+cloquintocet-mexyl, and a compound of formula (I)+clodinafop-propargyl+cloquintocet-mexyl.

[0403] Various aspects and embodiments of the present invention will now be illustrated in more detail by way of example. It will be appreciated that modification of detail may be made without departing from the scope of the invention.

[0404] For the avoidance of doubt, where a literary reference, patent application, or patent, is cited within the text of this application, the entire text of said citation is herein incorporated by reference.

EXAMPLES

Example 1

Synthesis of 2-cyclopropyl-4,5-dichloro-6-methoxycarbonyl pyrimidine

1.1 Preparation of Cyclopropylcarboxamidine Hydrochloride Salt

##STR00097##

[0406] Hydrogen chloride gas was bubbled through a stirred solution of cyclopropylcarbonitrile (10.0 g, 0.15 mol) and methanol (6 ml, 0.15 mol) in dry ether (60 ml) at 0.degree. C. for 2 hours. The reaction mixture was evaporated under reduced pressure and the residue dissolved in methanol (125 ml). The solution was added to an ice-cold mixture of methanol (125 ml) and liquid ammonia (15 ml) and the mixture stirred for 1 hour. The resulting clear solution was evaporated to leave cyclopropylcarboxamidine hydrochloride salt as a white solid (12.0 g, 67%).

[0407] .sup.1H nmr (400 MHz, d.sub.6-DMSO) .delta..sub.H 8.75 (2H, s), 8.64 (2H, s), 1.81 (1H, quintet), 1.11 (4H, s) ppm.

1.2 Preparation of 2-cyclopropyl-4-hydroxypyrimidine-6-carboxylic acid

##STR00098##

[0409] A solution of sodium hydroxide (2.85 g, 71.3 mmol) in water (3 ml) was added to a stirred solution of diethyl oxaloacetate sodium salt (8.7 g, 50 mmol) in water (50 ml) and the mixture stirred for 20 minutes. Cyclopropylcarboxamidine hydrochloride salt (5.0 g, 40 mmol) was added to the solution and the mixture was heated at 70.degree. C. overnight, then cooled to ambient temperature and acidified to pH1 by the cautious addition of concentrated hydrochloric acid. The precipitate was isolated by filtration and dried to yield 2-cyclopropyl-4-hydroxypyrimidine-6-carboxylic acid (4.7 g, 63%).

[0410] .sup.1H nmr (400 MHz, d.sub.6-DMSO) .delta..sub.H 13.30 (1H, br s), 12.97 (1H, br s), 6.59 (1H, s), 1.94 (1H, quintet), 1.04 (4H, m) ppm.

1.3 Preparation of 5-chloro-2-cyclopropyl-4-hydroxypyrimidine-6-carboxylic acid

##STR00099##

[0412] Aqueous sodium hypochlorite (470 ml) was added to a solution of 2-cyclopropyl-4-hydroxypyrimidine-6-carboxylic acid (68.7 g, 0.38 mol) in concentrated hydrochloric acid (280 ml) and water (412 ml), maintaining the temperature below 15.degree. C. during the course of the addition. The reaction mixture was stirred for 12 hours at ambient temperature, then sodium metabisulphite (6.87 g) and sodium hydroxide (50% aqueous solution; 29.0 g) were added, maintaining the temperature below 15.degree. C. during the addition. The precipitate was removed by filtration and dried to provide 5-chloro-2-cyclopropyl-4-hydroxypyrimidine-6-carboxylic acid (54 g, 66%).

[0413] .sup.1H nmr (400 MHz, d.sub.6-DMSO) .delta..sub.H 14.10 (1H, br s), 13.43 (1H, br s), 1.95 (1H, m), 1.08 (2H, m), 1.04 (2H, m) ppm.

1.4 Preparation of 2-cyclopropyl-4,5-dichloropyrimidine-6-carboxylic acid

##STR00100##

[0415] A mixture of 5-chloro-2-cyclopropyl-4-hydroxypyrimidine-6-carboxylic acid (10.0 g, 40 mmol) and phosphorus oxychloride (21.5 ml) was heated at reflux for 12 hours. The mixture was allowed to cool to ambient temperature and then added carefully to iced water and the resulting mixture extracted with ether. The combined ether layers were washed successively with water and brine, dried over sodium sulphate, filtered and the filtrate evaporated under reduced pressure to provide 2-cyclopropyl-4,5-dichloropyrimidine-6-carboxylic acid as a brown solid (7.0 g, 64%).

[0416] .sup.1H nmr (400 MHz, d.sub.6-DMSO) .delta..sub.H 3.37 (1H, br s), 2.24 (1H, m), 1.16 (2H, m), 1.08 (2H, m) ppm.

1.5 Preparation of 2-cyclopropyl-4,5-dichloro-6-methoxycarbonylpyrimidine

##STR00101##

[0418] An excess of freshly prepared diazomethane was added to a solution of 2-cyclopropyl-4,5-dichloropyrimidine-6-carboxylic acid (50.0 g, 0.21 mol) in ether (1.5 l) at 0.degree. C. After stirring for 15 minutes the reaction mixture was concentrated under reduced pressure to leave a brown oil. The residue was purified by column chromatography on silica using 10% ethyl acetate in hexane as eluent to provide 2-cyclopropyl-4,5-dichloro-6-methoxycarbonylpyrimidine (45.0 g, 85%) as a yellow oil, which solidified upon cooling. .sup.1H nmr (400 MHz, d.sub.6-DMSO) .delta..sub.H 3.95 (3H, s), 2.25 (1H, quintet), 1.17 (2H, m), 1.03 (2H, m) ppm.

[0419] Further examples, prepared using the general method of Example 1, are given in Table 2 below.

TABLE-US-00010 TABLE 2 Compounds made according to the general method described in Example 1 above. Characteristic data is .sup.1H nmr data (400 MHz, CDCl.sub.3) .delta..sub.H ppm Name Structure Characteristic data 2-(4-Chloro-2-fluoro-3- methoxyphenyl)-4,5-dichloro-6- methoxycarbonylpyrimidine ##STR00102## 7.78 (1H, dd), 7.26 (1H, dd), 4.05 (3H, s), 4.01 (3H, s)

Example 2

Synthesis of 4-amino-5-chloro-2-cyclopropyl-6-methoxycarbonyl pyrimidine

##STR00103##

[0421] A mixture of 2-cyclopropyl-4,5-dichloro-6-methoxycarbonylpyrimidine (prepared as described in Example 1) (2.5 g, 10 mmol), ammonia (7M solution in methanol; 6 ml, 42 mmol) and methanol (8.3 ml) was heated in a microwave reactor at 120.degree. C. for 20 minutes, then allowed to cool to ambient temperature. The solvent was evaporated under reduced pressure and the residue recrystallised from methanol to provide a white solid. The solid was dissolved in chloroform and the resulting solution washed with water and brine, dried over magnesium sulphate, filtered and the filtrate evaporated under reduced pressure to provide 4-amino-5-chloro-2-cyclopropyl-6-methoxycarbonylpyrimidine as a white solid (0.77 g, 38%).

[0422] .sup.1H nm r (400 MHz, CDCl.sub.3) .delta..sub.H 5.40 (2H, br s), 4.00 (3H, s), 2.10 (1H, m), 1.10 (4H, m) ppm.

Example 3

Synthesis of 5-chloro-2-cyclopropyl-4-dimethylamino-6-methoxycarbonylpyrimidine

##STR00104##

[0424] A mixture of 2-cyclopropyl-4,5-dichloro-6-methoxycarbonylpyrimidine (prepared as described in example 1) (0.5 g, 2.0 mmol), dimethylamine hydrochloride (325 mg, 4.0 mmol), triethylamine (0.55 ml, 4.0 mmol) and dichloromethane (7 ml) was stirred at ambient temperature for 4 hours. Ethyl acetate was added and the solution washed with brine, dried over magnesium sulphate, filtered and the filtrate evaporated under reduced pressure to provide 5-chloro-2-cyclopropyl-4-dimethylamino-6-methoxycarbonyl-pyrimidine as a white solid (0.46 g, 90%).

[0425] .sup.1H nm r (400 MHz, CDCl.sub.3) .delta..sub.H 4.00 (3H, s), 3.20 (6H, s), 2.10 (1H, m), 1.00 (4H, m) ppm.

Example 4

synthesis of 4-amino-2,5-dichloro-6-methoxycarbonylpyrimidine

4.1 Preparation of 2,4-dihydroxy-6-methoxycarbonylpyrimidine (methyl orotate)

##STR00105##

[0427] Thionyl chloride (500 ml), pyridine (2.5 ml) and a few drops of dimethylformamide were added to orotic acid monohydrate (78 g, 0.44 mol). The reaction mixture was stirred at RT for 5 days and then heated under reflux for an additional 14 hours. After cooling the solid material was allowed to settle and the supernatant decanted. The solid residue was washed with hexane and dried. Methanol (700 ml) was added dropwise with agitation to the solid. Once the rate of the gas formation slowed, the mixture was heated at reflux overnight and then cooled to 4-5.degree. C. The solid was removed by filtration and washed with methanol and ether to provide methyl orotate (73 g, 97%).

[0428] .sup.1H nmr (400 MHz, d.sub.6-DMSO) .delta..sub.H 11.41 (1H, s), 11.26 (1H, s), 6.04 (1H, s), 3.84 (3H, s) ppm.

4.2 Preparation of 5-chloro-2,4-dihydroxy-6-methoxycarbonylpyrimidine

##STR00106##

[0430] A catalytic quantity of ferric chloride was added to a solution of methyl orotate (34 g, 0.20 mol) in acetic anhydride (5% solution in glacial acetic acid, 500 ml). The mixture was heated to 90-95.degree. C. and sulphuryl chloride (54 g, 0.40 mol) was added dropwise. After the addition was complete, the solution was slowly brought to reflux with agitation and heating was continued overnight. The solution was cooled to 18.degree. C. and the solid was removed by filtration. The solid was washed with acetic acid and then with water, and dried to give 5-chloro-2,4-dihydroxy-6-methoxycarbonylpyrimidine (36.0 g, 89%).

[0431] .sup.1H nmr (400 MHz, d.sub.6-DMSO) .delta..sub.H 11.86 (1H, s), 11.62 (1H, s), 3.88 (3H, s) ppm.

4.3 Preparation of 6-methoxycarbonyl-2,4,5-trichloropyrimidine

##STR00107##

[0433] Phosphorus oxychloride (993 ml) was added to 5-chloro-2,4-dihydroxy-6-methoxycarbonylpyrimidine (30.0 g, 0.146 mol) at 10.degree. C. and the resulting solution cooled to 0.degree. C. N,N-Diethyl aniline (30.9 ml, 0.193 mol) was added dropwise to the stirred solution. After the addition was complete, the reaction mixture was allowed to warm slowly to ambient temperature and was then heated at reflux overnight. The resulting solution was cooled and concentrated under reduced pressure. The residue was poured onto crushed ice (600 g) and extracted with cold ether. The ether extracts were washed with brine, dried over sodium sulphate, filtered and evaporated under reduced pressure to give a light brown solid. This was triturated with warm hexane to yield 6-methoxycarbonyl-2,4,5-trichloropyrimidine (28 g, 82%).

[0434] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 4.02 (3H, s) ppm.

4.4 Preparation of 4-amino-2,5-dichloro-6-methoxycarbonylpyrimidine

##STR00108##

[0436] Aqueous ammonia (30% solution; 8.0 ml, 0.42 mol) was added dropwise to a stirred solution of 6-methoxycarbonyl-2,4,5-trichloropyrimidine (20.0 g, 0.083 mol) in THF (1000 ml) at 0.degree. C. The reaction mixture was stirred at 0.degree. C. for 1 hour and then filtered. The filtrate was evaporated under reduced pressure to give a white solid that was washed with twice with hexane and dried under vacuum to provide 4-amino-2,5-dichloro-6-methoxycarbonylpyrimidine (15.0 g, 82%).

[0437] .sup.1H nmr (400 MHz, d.sub.6-DMSO) .delta..sub.H 8.57 (1H, br s), 7.94 (1H, br s), 3.88 (3H, s) ppm.

Example 5

Synthesis of 4-amino-5-chloro-6-methoxycarbonyl-2-(4-trifluoro-methylphenyl)-pyrimidin- e

##STR00109##

[0439] 4-Trifluoromethylphenyl boronic acid (190 mg, 1.0 mmol), 4-amino-2,5-dichloro-6-methoxycarbonylpyrimidine (prepared as described in example 4) (221 mg, 1.0 mmol), caesium fluoride (302 mg, 2.0 mmol) and [1,1'-bis(diphenylphosphino)-ferrocene] dichloropalladium (II) complex with dichloromethane (1:1) (82 mg, 0.10 mmol) were placed in a vial. The vial was evacuated and backfilled with nitrogen before adding dimethoxyethane (2 ml) and water (2 ml). The reaction mixture was heated in a microwave reactor at 140.degree. C. for 20 minutes, then allowed to cool and filtered through a plug of silica, washing with ethyl acetate. The filtrate was evaporated under reduced pressure and the crude product purified by chromatography on silica using a gradient of hexane/ethyl acetate (100:0 to 3:2) as eluent to provide 4-amino-5-chloro-6-methoxycarbonyl-2-(4-trifluoromethylphenyl)-pyrimidine as a pale yellow solid (102 mg, 31%).

[0440] M.p. 204-205.degree. C.; .sup.1H nm r (400 MHz, CDCl.sub.3) .delta..sub.H 8.50 (2H, d), 7.70 (2H, d), 5.60 (2H, br s), 4.00 (3H, s) ppm.

[0441] Further compounds, prepared using this general method, are listed in Table 3 below.

TABLE-US-00011 TABLE 3 Compounds made according to the general method described in Example 5 above. Characteristic data provided is either melting point (.degree. C.) and/or 1H-nmr data (400 MHz, CDCl.sub.3) .delta..sub.H ppm Characteristic Name Structure data 4-Amino-5- chloro-2-(4- chloro- phenyl)- 6-methoxy- carbonyl- pyrimidine ##STR00110## 8.30 (2H, d), 7.4 (2H, d), 5.5 (2H, br s), 4.00 (3H, s) 4-Amino-5- chloro-2-(4- chloro-2- fluoro-3- methoxy- phenyl)-6- methoxy- carbonyl- pyrimidine ##STR00111## 141-142 4-Amino-5- chloro-2-(4- chloro-3- dimethyl- amino-2- fluoro- phenyl)- 6-methoxy- carbonyl- pyrimidine ##STR00112## 7.60 (1H, dd), 7.20 (1H, dd), 5.70 (2H, br s), 4.00 (3H, s), 2.9 (6H, s)

Example 6

Synthesis of 4-amino-2-cyclopropyl-6-methoxycarbonyl-4-methylpyrimidine (compound 2-41)

##STR00113##

[0443] A mixture of methyl boronic acid (45 mg, 0.75 mmol), 4-amino-2,5-dichloro-6-methoxycarbonylpyrimidine (prepared as described in example 4) (114 mg, 0.50 mmol), palladium acetate (11 mg, 0.05 mmol), sodium 2-(dicyclohexylphosphino)-2',6'-dimethoxybiphenyl-3'-sulphonate (38 mg, 0.075 mmol), potassium phosphate (212 mg, 1 mmol), toluene (2 ml) and water (0.4 ml) was heated in a microwave reactor at 110.degree. C. for 40 minutes. The reaction mixture was allowed to cool and the solvent evaporated under reduced pressure. The residue was purified by chromatography on silica with 40% ethyl acetate in hexane as eluent to provide 4-amino-2-cyclopropyl-6-methoxycarbonyl-4-methylpyrimidine as an orange solid (27 mg, 26%).

[0444] M.p. 152-153.degree. C.; .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 4.92 (2H, br s), 3.95 (3H, s), 2.18 (3H, s), 2.07 (1H, m), 1.03 (2H, m), 0.95 (2H, m) ppm.

[0445] Further compounds, prepared using this general method, are listed in Table 4 below.

TABLE-US-00012 TABLE 4 Compounds made according to the general method described in Example 6 above. Characteristic data provided is either melting point (.degree. C.) and/or 1H- nmr data (400 MHz, CDCl.sub.3) .delta..sub.H ppm Compound Number Name Structure Characteristic data 5-41 4-Amino-2-(4- chlorophenyl)-6- methoxycarbonyl- 4- methylpyrimidine ##STR00114## 206-208 27-41 4-Amino-2-(4- chloro-2-fluoro-3- methoxyphenyl)- 6- methoxycarbonyl- 4- methylpyrimidine ##STR00115## 7.60 (1H, t), 7.20 (1H, d), 5.10 (2H, br s), 4.00 (3H, s), 3.95 (3H, s), 2.30 (3H, s) 60-41 4-Amino-2-(2- fluoro-3-methoxy- 4-methylphenyl)- 6- methoxycarbonyl- 4- methylpyrimidine ##STR00116## 7.50 (1H, t), 7.00 (1H, d), 5.10 (2H, br s), 3.95 (3H, s), 3.90 (3H, s), 2.30 (3H, s), 2.25 (3H, s) 33-41 4-Amino-2-(4- chloro-3- dimethylamino-2- fluorophenyl)-6- methoxycarbonyl- 4- methylpyrimidine ##STR00117## 7.60 (1H, t), 7.20 (1H, dd), 5.20 (2H, br s), 3.90 (3H, s), 2.90 (6H, s), 2.30 (3H, s)

Example 7

Synthesis of 4-amino-2-(4-chloro-3-dimethylamino-2-fluorophenyl)-5-cyclopropyl-6-metho- xycarbonylpyrimidine (compound 33-58)

##STR00118##

[0447] A mixture of 4-amino-5-chloro-2-(4-chloro-3-dimethylamino-2-fluorophenyl)-6-methoxycar- bonylpyrimidine (prepared as described in example 5) (500 mg, 1.4 mmol), cyclopropyl boronic acid (144 mg, 1.68 mmol), palladium acetate (16 mg, 0.072 mmol), tricyclohexylphosphine tetrafluoroborate (52 mg, 0.14 mmol), potassium phosphate (890 mg, 4.2 mmol), toluene (9 ml) and water (1 ml) was purged with nitrogen, then heated in a microwave reactor at 160.degree. C. for 30 minutes. The reaction mixture was allowed to cool, water added and the resulting mixture extracted with dichloromethane. The organic phase was washed with brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure. The residue was purified by chromatography on silica using hexane/ethyl acetate (first 8:2, then 6:4) as eluent to provide 4-amino-2-(4-chloro-3-dimethylamino-2-fluorophenyl)-5-cyclopropyl-6-metho- xycarbonylpyrimidine as an off-white solid (178 mg, 35%).

[0448] M.p. 156-158.degree. C.; .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 7.60 (1H, t), 7.20 (1H, dd), 5.50 (2H, br s), 4.00 (3H, s), 2.90 (6H, s), 1.70 (1H, m), 1.00 (2H, m), 0.60 (2H, m) ppm.

[0449] Further examples, prepared using this general method, are listed in Table 5 below.

TABLE-US-00013 TABLE 5 Compounds made according to the general method described in Example 7 above. Characteristic data is .sup.1H nmr data (400 MHz, CDCl.sub.3) .delta..sub.H ppm Compound No. Name Structure Characteristic data 27-58 4-Amino-2-(4-chloro-2- fluoro-3- methoxyphenyl)-5- cyclopropyl-6- methoxycarbonyl- pyrimidine ##STR00119## 7.60 (1H, t), 7.20 (1H, dd), 5.50 (2H, br s), 4.00 (6H, s), 1.70 (1H, m), 1.00 (2H, m), 0.60 (2H, m)

Example 8

Synthesis of 5-amino-2-(4-chloro-3-dimethylamino-2-fluorophenyl)-6-ethenyl-6-methoxyca- rbonylpyrimidine (compound 33-61)

##STR00120##

[0451] Vinyl boronic acid pinacol ester (86 .mu.l, 0.51 mmol), 4-amino-5-chloro-2-(4-chloro-3-dimethylamino-2-fluorophenyl)-6-methoxycar- bonyl-pyrimidine (prepared as described in example 5) (165 mg, 0.46 mmol), caesium fluoride (139 mg, 0.92 mmol) and [1,1'-bis(diphenylphosphino)-ferrocene] dichloropalladium (II) complex with dichloromethane (1:1) (38 mg, 46 .mu.mol) were placed in a vial. The vial was evacuated and backfilled with nitrogen before adding dimethoxyethane (2 ml) and water (2 ml). The reaction mixture was heated in a microwave reactor at 140.degree. C. for 20 minutes, then allowed to cool and filtered through a plug of silica, washing with ethyl acetate. The filtrate was evaporated under reduced pressure and the crude product purified by chromatography on silica using a gradient of hexane/ethyl acetate (100:0 to 8:2) as eluent to provide 5-amino-2-(4-chloro-3-dimethylamino-2-fluorophenyl)-5-ethenyl-6-methoxyca- rbonylpyrimidine as a solid (68 mg, 42%).

[0452] M.p. 136-137.degree. C.; .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 7.60 (1H, t), 7.20 (1H, dd), 6.80 (1H, dd), 5.70 (2H, m), 5.40 (2H, br s), 3.90 (3H, s), 2.90 (6H, s) ppm.

[0453] Further compounds, prepared using this general method, are listed in Table 6 below.

TABLE-US-00014 TABLE 6 Compounds made according to the general method described in Example 8 above. Characteristic data provided is either melting point (.degree. C.) and/or 1H- nmr data (400 MHz, CDCl.sub.3) .delta..sub.H ppm Compound No. Name Structure Characteristic data 2-61 4-Amino-2- cyclopropyl-5- ethenyl-6- methoxycarbonyl- pyrimidine ##STR00121## 6.74 (1H, dd), 5.60 (1H, dd), 5.50 (1H, dd), 5.18 (2H, br s), 3.91 (3H, s), 2.10 (1H, m), 1.05 (2H, m), 0.97 (2H, m) 5-61 4-Amino-2-(4- chlorophenyl)-5- ethenyl-6- methoxycarbonyl- pyrimidine ##STR00122## 165-167 2-64 4-Amino-2- cyclopropyl-6- methoxycarbonyl- 5-(prop-1-en-2- yl)-pyrimidine ##STR00123## 140-142 2-65 4-Amino-2- cyclopropyl-6- methoxycarbonyl- 5-(pent-1-enyl)- pyrimidine ##STR00124## 6.30 (1H, d), 5.90 (1H, dd), 5.10 (2H, br s), 3.90 (3H, s), 2.20 (2H, m), 2.10 (1H, m), 1.50 (2H, m), 1.10 (2H, m), 0.90 (5H, m) 2-66 4-Amino-2- cyclopropyl-5-(2- cyclopropyl- ethenyl)-6- methoxycarbonyl- pyrimidine ##STR00125## 156-157 2-62 (Z isomer) (Z)-4-Amino-2- cyclopropyl-6- methoxycarbonyl- 5-(prop-1-enyl)- pyrimidine ##STR00126## 120-121 2-62 (E isomer) (E)-4-Amino-2- cyclopropyl-6- methoxycarbonyl- 5-(prop-1-enyl)- pyrimidine ##STR00127## 147-148 27-61 4-Amino-2-(4- chloro-2-fluoro-3- methoxyphenyl)- 5-ethenyl-6- methoxycarbonyl- pyrimidine ##STR00128## 146-148 2-77 4-Amino-2- cyclopropyl-5- (3,3-dimethylbut- 1-ynyl)-6- methoxycarbonyl- pyrimidine ##STR00129## 5.40 (2H, br s), 3.90 (3H, s), 2.10 (1H, m), 1.30 (9H, s), 1.10 (2H, m), 0.90 (2H, m) 27-62 (E isomer) (E)-4-Amino-2-(4- chloro-2-fluoro-3- methoxyphenyl)- 6- methoxycarbonyl- 5-(prop-1-enyl)- pyrimidine ##STR00130## 7.60 (1H, t), 7.20 (1H, d), 6.60 (1H, dd), 6.10 (1H, m), 5.30 (2H, br s), 4.00 (3H, s), 3.90 (3H, s), 1.90 (3H, d) 31-61 4-Amino-5- ethenyl-6- methoxycarbonyl- 2-(4- trifluoromethyl- phenyl)-pyrimidine ##STR00131## 137-139 33-62 (E isomer) (E)-4-Amino-2-(4- chloro-3- dimethylamino-2- fluorophenyl)-6- methoxycarbonyl- 5-(prop-1-enyl)- pyrimidine ##STR00132## 136-137 27-62 (Z isomer) (Z)-4-Amino-2-(4- chloro-2-fluoro-3- methoxyphenyl)- 6- methoxycarbonyl- 5-(prop-1-enyl)- pyrimidine ##STR00133## 7.70 (1H, t), 7.30 (1H, dd), 6.40 (1H, dd), 6.10 (1H, m), 5.30 (2H, br s), 4.00 (3H, s), 3.90 (3H, s), 1.60 (3H, dd) 2-221 2-Cyclopropyl-4- dimethylamino-6- methoxycarbonyl- 5- methylpyrimidine ##STR00134## 4.00 (3H, s), 3.00 (6H, s), 2.30 (3H, s), 2.10 (1H, m), 1.00 (4H, m) 2-225 2-Cyclopropyl-4- dimethylamino-5- ethenyl-6- methoxycarbonyl- pyrimidine ##STR00135## 6.80 (1H, dd), 5.30 (2H, dd), 3.90 (3H, s), 3.10 (6H, s), 2.10 (1H, m), 1.00 (4H, m) 27-63 4-Amino-2-(4- chloro-2-fluoro-3- methoxyphenyl)- 6- methoxycarbonyl- 5-(prop-1-en-2- yl)-pyrimidine ##STR00136## 7.60 (1H, t), 7.20 (1H, dd), 5.40 (1H, s), 5.30 (2H, br s), 5.10 (1H, s), 4.00 (3H, s), 3.90 (3H, s), 2.10 (3H, s) 27-69 4-Amino-2-(4- chloro-2-fluoro-3- methoxyphenyl)- 6- methoxycarbonyl- 5-(2-methylprop- 1-enyl)- pyrimidine ##STR00137## 7.70 (1H, t), 7.20 (1H, dd), 6.10 (1H, s), 5.30 (2H, br s), 4.00 (3H, s), 3.90 (3H, s) 2.00 (3H, s), 1.60 (3H, s) 2-69 4-Amino-2- cyclopropyl-6- methoxycarbonyl- 5-(2-methylprop- 1-enyl)- pyrimidine ##STR00138## 6.00 (1H, s), 5.00 (2H, br s), 3.90 (3H, s), 2.10 (1H, m), 1.9 (3H, s), 1.50 (3H, s), 1.10 (2H, m), 0.90 (2H, m). 33-62 (Z isomer) (Z)-4-Amino-2-(4- chloro-3- dimethylamino-2- fluorophenyl)-6- methoxycarbonyl- 5-(prop-1-enyl)- pyrimidine ##STR00139## 7.60 (1H, t), 7.20 (1H, d), 6.40 (1H, dd), 6.10 (1H, m), 5.40 (2H, m), 3.90 (3H, s), 2.90 (6H, s), 1.60 (3H, dd) 33-64 4-Amino-2-(4- chloro-3- dimethylamino-2- fluorophenyl)-6- methoxycarbonyl- 5-(prop-1-en-2- yl)-pyrimidine ##STR00140## 7.60 (1H, t), 7.20 (1H, dd), 5.40 (2H, br s), 5.40 (1H, m), 5.10 (1H, s), 3.90 (3H, s), 2.90 (6H, s), 2.10 (3H, s)

Example 9

Synthesis of 4-amino-6-methoxycarbonyl-5-prop-1-enyl-2-(4-tri-fluoromethylphenyl)-pyri- midine (compound 31-62)

##STR00141##

[0455] 4-Trifluoromethylphenyl boronic acid (190 mg, 1.0 mmol), 4-amino-2,5-dichloro-6-methoxycarbonylpyrimidine (prepared as described in example 4) (221 mg, 1.0 mmol), caesium fluoride (302 mg, 2.0 mmol) and [1,1'-bis(diphenylphosphino)-ferrocene] dichloropalladium (II) complex with dichloromethane (1:1) (82 mg, 0.10 mmol) were placed in a vial. The vial was evacuated and backfilled with nitrogen before adding dimethoxyethane (2 ml) and water (2 ml). The reaction mixture was heated in a microwave reactor at 140.degree. C. for 20 minutes, then allowed to cool and filtered through a plug of silica, washing with ethyl acetate. The filtrate was evaporated under reduced pressure and the residue dissolved in dimethoxyethane (2.5 ml) and water (2.5 ml). To this solution were added propenyl boronic acid (112 mg, 1.3 mmol), caesium fluoride (302 mg, 2.0 mmol) and [1,1'-bis(diphenylphosphino)-ferrocene] dichloropalladium (II) complex with dichloromethane (1:1) (82 mg, 0.10 mmol). The resulting mixture was heated in a microwave reactor at 140.degree. C. for 20 minutes, then allowed to cool and filtered through a plug of silica, washing with ethyl acetate. The filtrate was washed with brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure. The crude product was purified by chromatography on silica using a gradient of hexane/ethyl acetate (100:0 to 8:2) as eluent to provide 4-amino-6-methoxycarbonyl-5-prop-1-enyl-2-(4-trifluoromethylphenyl)-pyrim- idine as an off-white solid (145 mg, 43%).

[0456] M.p. 123-125.degree. C.; .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 8.50 (2H, d), 7.70 (2H, d), 6.40 (1H, dd), 6.10 (1H, dd), 5.30 (2H, br s), 3.90 (3H, s), 1.90 (3H, dd) ppm.

[0457] Further compounds, prepared using this general method, are listed in Table 7 below.

TABLE-US-00015 TABLE 7 Compounds made according to the general method described in Example 9 above. Characteristic data provided is either melting point (.degree. C.) and/or 1H- nmr data (400 MHz, CDCl.sub.3) .delta..sub.H ppm Compound No. Name Structure Characteristic data 31-64 4-Amino-6- methoxycarbonyl- 5-(prop-1-en-2- yl)-2-(4- trifluoromethyl- phenyl)-pyrimidine ##STR00142## 83-85 31-63 4-Amino-6- methoxycarbonyl- 5-(prop-1-en-3- yl)-2-(4- trifluoromethyl- phenyl)-pyrimidine ##STR00143## 8.50 (2H, d), 7.70 (2H, d), 5.90 (1H, m), 5.20 (4H, m + br s), 4.00 (3H, s), 3.50 (2H, m) 27-61 4-Amino-2-(4- chloro-2-fluoro-3- methoxyphenyl)- 5-ethenyl-6- methoxycarbonyl- pyrimidine ##STR00144## 146-148

Example 10

Synthesis of 4-amino-5-ethenyl-6-methoxycarbonyl-2-methylthiopyrimidine (compound 62-61)

10.1 Preparation of 4-amino-5-chloro-6-methoxycarbonyl-2-methylthiopyrimidine

##STR00145##

[0459] Sodium methanethiolate (3.0 g, 35 mmol) was added portionwise to a stirred solution of 4-amino-2,5-dichloro-6-methoxycarbonylpyrimidine (prepared as described in example 4) (4.4. g, 20 mmol) in methanol (100 ml) to give a pale yellow solution. The resulting mixture was stirred at reflux for 2 hours then allowed to cool for 2 hours, filtered and evaporated under reduced pressure. The residue was dissolved in water and ethyl acetate, the phases separated and the aqueous extracted with further ethyl acetate. The combined organic phases were washed with water and brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure to provide 4-amino-5-chloro-6-methoxycarbonyl-2-methylthiopyrimidine as a yellow solid (2.2 g), which was used without further purification.

[0460] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 5.55 (2H, br s), 3.95 (3H, s), 2.50 (3H, s) ppm.

10.2 Preparation of 4-amino-5-ethenyl-6-methoxycarbonyl-2-methylthiopyrimidine (compound 62-61)

##STR00146##

[0462] Water (2 ml) was added with stirring to a solution of 4-amino-5-chloro-6-methoxycarbonyl-2-methylthiopyrimidine (233 mg, 1.0 mmol) in dimethoxyethane (3 ml). The mixture was heated in a microwave reactor at 140.degree. C. for 2 hours, then allowed to cool, diluted with ethyl acetate and washed with water and brine. The organic phase was dried over magnesium sulphate, filtered and evaporated under reduced pressure to provide a brown oil which was purified by chromatography on silica using hexane/ethyl acetate (4:1) as eluent to provide 4-amino-5-ethenyl-6-methoxycarbonyl-2-methylthiopyrimidine as a beige solid (120 mg, 50%).

[0463] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 6.70 (1H, dd), 5.75 (2H, dd), 5.30 (2H, br s), 3.90 (3H, s), 2.50 (3H, s) ppm.

Example 11

Synthesis of 4-amino-5-ethenyl-6-methoxycarbonyl-2-(4-methylphenyl)-pyrimidine (compound 36-61)

##STR00147##

[0465] A solution of 4-amino-5-ethenyl-6-methoxycarbonyl-2-methylthiopyrimidine (prepared as described in example 10) (113 mg, 0.50 mmol), 4-methylphenylboronic acid (74 mg, 0.55 mmol), copper thiophene-2-carboxylate (125 mg, 0.65 mmol)), tri(2-furyl)phosphine (19 mg, 80 .mu.mol) and tris(dibenzylideneacetone)dipalladium chloroform adduct (10 mg, 10 .mu.mol) in tetrahydrofuran (3 ml) was heated in a microwave reactor at 100.degree. C. for 30 minutes, then allowed to cool. Ether was added and the resulting solution washed with concentrated aqueous ammonia and brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure to provide a brown solid (0.13 g). The crude product was purified by chromatography on silica using hexane/ethyl acetate (4:1) as eluent to provide 4-amino-5-ethenyl-6-methoxycarbonyl-2-(4-methylphenyl)-pyrimidine as a pale yellow solid (45 mg, 33%).

[0466] M.p. 122-123.degree. C.; .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 8.24 (2H, d), 7.22 (2H, d), 6.80 (1H, dd), 5.60 (2H, m), 5.35 (2H, br s), 3.93 (3H, s), 2.39 (3H, s) ppm.

[0467] Further compounds, prepared using this general method, are listed in Table 8 below.

TABLE-US-00016 TABLE 8 Compounds made according to the general method described in Example 11 above. Characteristic data provided is either melting point (.degree. C.) and/or 1H-nmr data (400 MHz, CDCl.sub.3) .delta..sub.H ppm Compound No. Name Structure Characteristic data 19-61 4-Amino-2-(4- chloro-3- fluorophenyl)-5- ethenyl-6- methoxycarbonyl- pyrimidine ##STR00148## 155-156 61-61 4-Amino-2-(3- chloro-5- fluorophenyl)-5- ethenyl-6- methoxycarbonyl- pyrimidine ##STR00149## 158-159 15-61 4-Amino-2-(4- chloro-2- fluorophenyl)-5- ethenyl-6- methoxycarbonyl- pyrimidine ##STR00150## 137-138 63-61 4-Amino-5- ethenyl-6- methoxycarbonyl- 2-(3,4,5- trifluorophenyl)- pyrimidine ##STR00151## 188-190 9-61 4-Amino-2-(3,4- dichlorophenyl)- 5-ethenyl-6- methoxycarbonyl- pyrimidine ##STR00152## 8.49 (1H, d), 8.22 (1H, dd), 7.50 (1H, d), 6.79 (1H, dd), 5.78 (1H, m), 5.64 (1H, dd), 5.40 (2H, br s), 3.98 (3H, s) 14-61 4-Amino-2-(4- chloro-3- trifluoromethyl- phenyl)-5-ethenyl-6- methoxycarbonyl- pyrimidine ##STR00153## 8.72 (1H, d), 8.49 (1H, dd), 7.56 (1H, d), 6.78 (1H, dd), 5.69 (1H, m), 5.65 (1H, dd), 5.42 (2H, br s), 3.97 (3H, s) 6-61 4-Amino-2-(4- bromophenyl)-5- ethenyl-6- methoxycarbonyl- pyrimidine ##STR00154## 8.25 (2H, d), 7.56 (2H, d), 6.79 (1H, dd), 5.66 (1H, m), 5.63 (1H, dd), 5.38 (2H, br s), 3.96 (3H, s) 41-61 4-Amino-5- ethenyl-2-(4- fluorophenyl)-6- methoxycarbonyl- pyrimidine ##STR00155## 8.37 (2H, d), 7.11 (2H, m), 6.80 (1H, dd), 5.65 (1H, m), 5.62 (1H, dd), 5.37 (2H, br s), 3.96 (3H, s) 44-61 4-Amino-2-(3- chloro-4- fluorophenyl)-5- ethenyl-6- methoxycarbonyl- pyrimidine ##STR00156## 8.46 (1H, dd), 8.27 (1H, m), 7.19 (1H, t), 6.79 (1H, dd), 5.67 (1H, m), 5.63 (1H, dd), 5.39 (2H, br s), 3.96 (3H, s) 43-61 4-Amino-5- ethenyl-2-(4- fluoro-3- trifluoromethyl- phenyl)-6- methoxycarbonyl- pyrimidine ##STR00157## 8.67 (1H, dd), 8.59 (1H, m), 7.25 (1H, t), 6.80 (1H, dd), 5.68 (1H, m), 5.64 (1H, dd), 5.41 (2H, br s), 3.97 (3H, s) 45-61 4-Amino-5- ethenyl-2-(4- fluoro-3- methylphenyl)-6- methoxycarbonyl- pyrimidine ##STR00158## 8.22 (1H, m), 8.18 (1H, m), 7.05 (1H, t), 6.79 (1H, dd), 5.66 (1H, m), 5.62 (1H, dd), 5.36 (2H, br s), 3.96 (3H, s), 2.34 (3H, s) 42-61 4-Amino-5- ethenyl-2-(4- fluoro-3- methoxyphenyl)- 6- methoxycarbonyl- pyrimidine ##STR00159## 8.02 (1H, dd), 7.97 (1H, m), 7.13 (1H, dd), 6.79 (1H, dd), 5.67 (1H, m), 5.63 (1H, d), 5.37 (2H, br s), 4.00 (3H, s), 3.96 (3H, s) 67-61 4-Amino-2-(3,4- difluorophenyl)-5- ethenyl-6- methoxycarbonyl- pyrimidine ##STR00160## 8.22 (1H, m), 8.15 (1H, m), 7.21 (1H, q), 6.80 (1H, dd), 5.67 (1H, d), 5.64 (1H, d), 5.38 (2H, br s), 3.97 (3H, s) 68-61 4-Amino-2-(4- cyanophenyl)-5- ethenyl-6- methoxycarbonyl- pyrimidine ##STR00161## 8.49 (2H, d), 7.74 (2H, d), 6.82 (1H, dd), 5.70 (1H, m), 5.66 (1H, dd), 5.41 (2H, br s), 3.97 (3H, s) 69-61 4-Amino-5- ethenyl-6- methoxycarbonyl- 2-(4- methoxycarbonyl- phenyl)- pyrimidine ##STR00162## 165-166 47-61 4-Amino-5- ethenyl-6- methoxycarbonyl- 2-(4- trifluoromethoxy- phenyl)-pyrimidine ##STR00163## 8.40 (2H, d), 7.27 (2H, d), 6.80 (1H, dd), 5.66 (1H, d), 5.63 (1H, d), 5.41 (2H, br s), 3.96 (3H, s) 71-61 4-Amino-5- ethenyl-2-(3,4- ethylenedioxy- phenyl)-6- methoxycarbonyl- pyrimidine ##STR00164## 7.92 (1H, d), 7.88 (1H, dd), 6.90 (1H, d), 6.79 (1H, dd), 5.63 (1H, s), 5.59 (1H, d), 5.36 (2H, br s), 4.30 (4H, m), 3.94 (3H, s) 30-61 4-Amino-2-(4- chloro-3,5- difluorophenyl)-5- ethenyl-6- methoxycarbonyl- pyrimidine ##STR00165## 8.04 (2H, m), 6.79 (1H, dd), 5.66 (2H, m), 5.40 (2H, br s), 3.95 (3H, s) 26-61 4-Amino-2-(4- chloro-3- methoxyphenyl)- 5-ethenyl-6- methoxycarbonyl- pyrimidine ##STR00166## 7.97 (1H, d), 7.95 (1H, dd), 7.42 (1H, d), 6.78 (1H, dd), 5.66 (1H, m), 5.63 (1H, dd), 5.39 (2H, br s), 4.03 (3H, s), 3.95 (3H, s) 70-61 4-Amino-5- ethenyl-6- methoxycarbonyl- 2-(3,4- methylenedioxy- phenyl)-pyrimidine ##STR00167## 7.97 (1H, dd), 7.84 (1H, d), 6.88 (1H, d), 6.78 (1H, dd), 6.03 (2H, s), 5.84 (2H, br s), 5.67 (1H, dd), 5.63 (1H, dd), 3.96 (3H, s) 72-61 4-Amino-5- ethenyl-6- methoxycarbonyl- 2-(4- methylthiophenyl)- pyrimidine ##STR00168## 8.28 (2H, d), 7.27 (2H, d), 6.78 (1H, dd), 5.64 (1H, s), 5.59 (1H, d), 5.44 (2H, br s), 3.95 (3H, s), 2.53 (3H, s) 73-61 4-Amino-5- ethenyl-6- methoxycarbonyl- 2-(2-naphthyl)- pyrimidine ##STR00169## 8.91 (1H, s), 8.47 (1H, d), 7.96 (1H, m), 7.88 (1H, d), 7.85 (1H, m), 7.49 (2H, m), 6.80 (1H, dd), 5.63 (2H, m), 5.45 (2H, br s), 3.98 (3H, s)

Example 12

Synthesis of 4-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-ethenylpyrimidine-6-carbo- xylic acid (compound 27-21)

##STR00170##

[0469] Sodium hydroxide (24 mg, 2 mmol) was added to a suspension of 4-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-ethenyl-6-methoxycarbonyl- pyrimidine (prepared as described in example 8) (100 mg, 0.30 mmol) in tetrahydrofuran (10 ml) and water (6.5 ml) The reaction mixture was stirred for 3 hours at ambient temperature then acidified to pH 1-2 and washed with ethyl acetate. The aqueous phase was concentrated under reduced pressure to provide an off white solid which was purified using a FractionLynx automated hplc system to yield 4-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-ethenylpyrimidine-6-carbo- xylic acid as a white solid (28 mg, 29%)

[0470] .sup.1H nm r (400 MHz, d.sub.6-DMSO) .delta..sub.H 7.50 (1H, m), 7.30 (1H, d), 6.50 (1H, m), 5.80 (1H, d), 5.30 (1H, d), 3.80 (3H, s) (amine and acid protons not observed).

[0471] Further examples, prepared using this general method, are listed in Table 9 below.

TABLE-US-00017 TABLE 9 Compounds made according to the general method described in Example 12 above. Characteristic data is .sup.1H nmr data (400 MHz, d.sub.6- DMSO) .delta..sub.H ppm Compound No. Name Structure Characteristic data 33-21 4-Amino-2-(4-chloro-3- dimethylamino-2- fluorophenyl)-5- ethenylpyrimidine-6- carboxylic acid ##STR00171## 7.50 (1H, t), 7.20 (1H, t), 6.50 (3H, br s and t), 5.70 (1H, d), 5.20 (1H, d), 2.40 (6h, d) (acid proton not observed)

Example 13

synthesis of 4-amino-2-(4-chloro-3-dimethylamino-2-fluorophenyl)-5-ethenyl-6-ethoxycar- bonyl-pyrimidine (compound 33-101)

##STR00172##

[0473] A solution of 4-amino-2-(4-chloro-3-dimethylamino-2-fluorophenyl)-5-ethenyl-6-methoxyca- rbonyl-pyrimidine (prepared by the method described in example 8) (200 mg, 0.57 mmol), 1-hydroxy-3-isothionato-1,1,3,3-tetrabutyl distannoxane (32 mg, 0.057 mmol), and ethanol (0.22 ml, 5.7 mmol) in toluene (8 ml) was heated at reflux for 3 hours. The reaction was allowed to cool and evaporated under reduced pressure and the residue purified by chromatography on silica using a hexane/ethyl acetate gradient (8:2 to 6:4) as eluent to provide 4-amino-2-(4-chloro-3-dimethylamino-2-fluorophenyl)-5-ethenyl-6-ethoxycar- bonyl-pyrimidine as a white solid (193 mg, 93%).

[0474] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 7.60 (1H, t), 7.20 (1H, dd), 6.80 (1H, dd), 5.70 (2H, dd), 5.50 (2H, br s), 4.40 (2H, q), 2.90 (6H, d), 1.40 (3H, t) ppm.

[0475] Further examples, prepared using this general method, are listed in Table 10 below.

TABLE-US-00018 TABLE 10 Compounds made according to the general method described in Example 13 above. Characteristic data is .sup.1H nmr data (400 MHz, CDCl.sub.3) .delta..sub.H ppm Compound Characteristic No. Name Structure data 33-306 4-Amino-2-(4- chloro-3- dimethylamino-2- fluorophenyl)-5- ethenyl-6- isopropoxycarbon- yl-pyrimidine ##STR00173## 7.62 (1H, t), 7.21 (1H, dd), 6.72 (1H, dd), 5.67 (1H, m), 5.64 (1H, m), 5.36 (2H, br s), 5.28 (1H, septet), 2.90 (6H, d), 1.37 (6H, d) 33-316 4-Amino-2-(4- chloro-3- dimethylamino-2- fluorophenyl)-5- ethenyl-6- .sup.npropoxycarbonyl- pyrimidine ##STR00174## 7.61 (1H, t), 7.22 (1H, dd), 6.76 (1H, dd), 5.68 (1H, s), 5.64 (1H, d), 5.42 (2H, br s), 4.31 (2H, t), 2.91 (6H, d), 1.80 (2H, sextet), 1.03 (3H, t) 33-391 4-Amino-6- .sup.nbutoxycarbonyl-2- (4-chloro-3- dimethylamino-2- fluorophenyl)-5- ethenyl-pyrimidine ##STR00175## 7.62 (1H, t), 7.22 (1H, dd), 6.77 (1H, dd), 5.68 (1H, s), 5.65 (1H, d), 5.39 (2H, br s), 4.36 (2H, t), 2.90 (6H, d), 1.76 (2H, m), 1.46 (2H, m), 0.96 (3H, t) 33-326 4-Amino-2-(4- chloro-3- dimethylamino-2- fluorophenyl)-5- ethenyl-6-(2- methylpropoxy) carbonyl-pyrimidine ##STR00176## 7.62 (1H, dd), 7.22 (1H, dd), 6.77 (1H, dd), 5.68 (1H, s), 5.64 (1H, d), 5.40 (2H, br s), 4.22 (1H, dd), 4.13 (1H, dd), 2.90 (6H, d), 1.93 (1H, m), 1.00 (3H, d), 0.92 (3H, t) 33-392 4-Amino-2-(4- chloro-3- dimethylamino-2- fluorophenyl)-5- ethenyl-6- .sup.noctyloxycarbonyl- pyrimidine ##STR00177## 7.61 (1H, dd), 7.22 (1H, dd), 6.77 (1H, dd), 5.78 (1H, s), 5.64 (1H, d), 5.40 (2H, br s), 5.35 (2H, t), 2.90 (6H, d), 1.76 (2H, quintet), 1.43 (2H, m), 1.30 (8H, m), 0.88 (3H, m) 33-393 4-Amino-2-(4- chloro-3- dimethylamino-2- fluorophenyl)-5- ethenyl-6-(2- ethylhexyloxy) carbonyl-pyrimidine ##STR00178## 7.63 (1H, t), 7.21 (1H, dd), 6.76 (1H, dd), 5.68 (1H, m), 5.64 (1H, m), 5.38 (2H, br s), 4.26 (2H, m), 2.90 (6H, d), 1.72 (1H, m), 1.37 (8H, m), 1.27 (3H, t), 0.92 (3H, m) 33-336 4-Amino-2-(4- chloro-3- dimethylamino-2- fluorophenyl)-5- ethenyl-6- phenylmethoxy- carbonyl-pyrimidine ##STR00179## 7.61 (1H, dd), 7.45 (2H, m), 7.36 (3H, m), 7.21 (1H, dd), 6.70 (1H, dd), 5.60 (1H, d), 5.56 (1H, s), 5.39 (4H, br s), 2.91 (6H, d) 33-394 4-Amino-2-(4- chloro-3- dimethylamino-2- fluorophenyl)-5- ethenyl-6-(1- phenyl- ethoxy)carbonyl- pyrimidine ##STR00180## 7.65 (1H, t), 7.45 (2H, m), 7.35 (3H, m), 7.22 (1H, dd), 6.64 (1H, dd), 6.14(1H, q), 5.59 (1H, d), 5.53(1H, dd), 5.38 (2H, br s), 2.91 (6H, d), 1.69 (3H, d) 33-395 4-Amino-2-(4- chloro-3- dimethylamino-2- fluorophenyl)-5- ethenyl-6-(prop-2- enyloxy)carbonyl- pyrimidine ##STR00181## 7.61 (1H, t), 7.22 (1H, dd), 6.78 (1H, dd), 6.02 (1H, m), 5.68 (1H, d), 5.65 (1H, dd), 5.47 (1H, m), 5.43 (2H, br s), 5.31 (1H, m), 4.85 (2H, m), 2.91 (6H, d) 33-396 4-Amino-2-(4- chloro-3- dimethylamino-2- fluorophenyl)-5- ethenyl-6-(2- ethoxy- ethoxy)carbonyl- pyrimidine ##STR00182## 7.60 (1H, t), 7.22 (1H, dd), 6.79 (1H, dd), 5.69 (1H, d), 5.65 (1H, m), 5.41 (2H, br s), 4.50 (2H, m), 3.76 (2H, m), 3.58 (2H, q), 2.90 (6H, d), 1.25 (3H, t) 33-397 4-Amino-6-(2- .sup.nbutoxy- ethoxy)carbonyl-2- (4-chloro-3- dimethylamino-2- fluorophenyl)-5- ethenyl-pyrimidine ##STR00183## 7.52 (1H, t), 7.24 (1H, dd), 6.77 (1H, dd), 5.75 (2H, m), 4.50 (2H, m), 3.75 (2H, m), 3.51 (2H, t), 3.29 (2H, br s), 2.91 (6H, d), 1.57 (2H, m), 1.38 (2H, m), 0.92 (3H, t)

Example 14

Synthesis of 4-amino-2-cyclopropyl-6-methoxycarbonyl-5-(trimethylsilylethynyl)-pyrimid- ine (compound 2-78)

##STR00184##

[0477] Palladium tetrakis(triphenylphosphine) (231 mg, 0.20 mmol) was added to a degassed solution of 4-amino-5-chloro-2-cyclopropyl-6-methoxycarbonylpyrimidine (prepared as described in example 2) (227 mg, 1.0 mmol) and trimethylsilylacetylene (0.28 ml, 2.0 mmol) in diisopropylamine (8 ml) and fluorobenzene (20 ml). The resulting solution was heated under nitrogen at 80.degree. C. for 32 hours, then allowed to cool and the solvent evaporated under reduced pressure. The residue was dissolved in dichloromethane, washed with water and brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure. The crude material was purified by high pressure liquid chromatography to provide 4-amino-2-cyclopropyl-6-methoxycarbonyl-5-(trimethylsilylethynyl)-pyrimid- ine as a white solid (15 mg, 5%).

[0478] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 5.50 (2H, br s), 3.95 (3H, s), 2.10 (1H, m), 1.10 (2H, m), 1.00 (2H, m), 0.30 (9H, s) ppm.

Example 15

Synthesis of 4-amino-2-chloro-6-methoxycarbonyl-5-prop-1-ynyl-pyrimidine (compound 1-74)

15.1 Preparation of 2,4-dichloro-5-iodo-6-methoxycarbonylpyrimidine

##STR00185##

[0480] A mixture of 2,4-dihydroxy-5-iodo-6-methoxycarbonylpyrimidine (1.0 g, 3.38 mmol), phosphorus oxychloride (6 ml) and dimethylformamide (0.1 ml) was heated at reflux for 3 hours, then allowed to cool to room temperature, concentrated under reduced pressure and poured into iced water. The resulting mixture was extracted with dichloromethane and the combined organic extracts washed with brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure. The residue was purified by chromatography on silica using a gradient of hexane/ethyl acetate (8:2 to 6:4) as eluent to provide 2,4-dichloro-5-iodo-6-methoxycarbonylpyrimidine as a brown solid (520 mg, 46%).

[0481] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 4.00 (3H, s) ppm.

15.2 Preparation of 4-amino-2-chloro-5-iodo-6-methoxycarbonylpyrimidine

##STR00186##

[0483] A solution of 2,4-dichloro-5-iodo-6-methoxycarbonylpyrimidine (950 mg, 2.86 mmol) and ammonia (7M in methanol; 1.6 ml, 11 mmol) in anhydrous dioxane (10 ml) was stirred at ambient temperature for 30 minutes then evaporated under reduced pressure. The residue was dissolved in ethyl acetate, washed with water, dried over magnesium sulphate, filtered and evaporated under reduced pressure. The residue was purified by chromatography on silica using a gradient of hexane/ethyl acetate (9:1 to 6:4) as eluent to provide 4-amino-2-chloro-5-iodo-6-methoxycarbonylpyrimidine as a white solid (590 mg, 66%).

[0484] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 5.90 (2H, br s), 4.00 (3H, s) ppm.

15.3 Preparation of 4-amino-2-chloro-6-methoxycarbonyl-5-prop-1-ynyl-pyrimidine (compound 1-74)

##STR00187##

[0486] A solution of 4-amino-2-chloro-5-iodo-6-methoxycarbonylpyrimidine (210 mg, 0.67 mmol), 1-tributylstannyl-propyne (0.3 ml, 1 mmol) and bis(triphenylphosphine)palladium dichloride (48 mg, 0.067 mmol) in dimethylformamide (6 ml) was heated in a microwave reactor at 160.degree. C. for 20 minutes, then allowed to cool. Ethyl acetate was added and the resulting solution washed with water and brine, dried over magnesium sulphate, filtered and evaporated. The residue was purified by chromatography using a gradient of hexane/ethyl acetate (9:1 to 2:8) as eluent to provide 4-amino-2-chloro-6-methoxycarbonyl-5-prop-1-ynyl-pyrimidine as a white solid (90 mg, 63%).

[0487] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 4.00 (3H, s), 2.20 (3H, s) ppm (amine protons not observed).

Example 16

Synthesis of 4-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-6-methoxycarbonyl-5-prop-1-- ynyl-pyrimidine (compound 27-74)

##STR00188##

[0489] 4-Chloro-2-fluoro-3-methoxyphenyl boronic acid (232 mg, 1.13 mmol), 4-amino-2-chloro-6-methoxycarbonyl-5-prop-1-ynyl-pyrimidine (prepared as described in example 15) (170 mg, 0.76 mmol), caesium fluoride (228 mg, 1.5 mmol) and [1,1'-bis(diphenylphosphino)-ferrocene] dichloropalladium (II) complex with dichloromethane (1:1) (62 mg, 0.075 mmol) were placed in a vial. The vial was evacuated and backfilled with nitrogen before adding dimethoxyethane (5 ml) and water (5 ml). The reaction mixture was heated in a microwave reactor at 140.degree. C. for 20 minutes, then allowed to cool. Dichloromethane was added and the solution washed with water, dried over magnesium sulphate, filtered and evaporated under reduced pressure. The crude product was purified by chromatography on silica using a gradient of hexane/ethyl acetate (9:1 to 3:2) as eluent to provide 4-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-6-methoxycarbonyl-5- -prop-1-ynyl-pyrimidine as a white solid (30 mg, 11%).

[0490] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 7.70 (1H, t), 7.20 (1H, dd), 5.80 (2H, br s), 4.00 (6H, s), 2.20 (3H, s) ppm.

Example 17

Synthesis of 4-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-6-formyl-6-methoxycarbonyl-- pyrimidine (compound 27-52)

##STR00189##

[0492] Ozone was bubbled through a stirred solution of 4-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-ethenyl-6-methoxycarbonyl- -pyrimidine (prepared by the method described in example 8) (125 mg, 0.0.37 mmol) in dichloromethane (40 ml) at -78.degree. C. until a blue colour persisted. Oxygen was then bubbled through the solution until it became colourless. Dimethyl sulphide (2 ml) was added and the solution allowed to warm to ambient temperature over 2 hours. The reaction mixture was evaporated under reduced pressure and the residue purified by chromatography on silica using a gradient of hexane/ethyl acetate (100:0 to 60:40) to provide 4-amino-2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-formyl-6-methoxycarbonyl-- pyrimidine as an off-white solid (50 mg, 40%).

[0493] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 10.40 (1H, s), 7.80 (1H, t), 7.20 (1H, m), 4.10 (3H, s), 4.00 (3H, s) ppm (amine protons not observed).

Example 18

Synthesis of 4-amino-5-(1-ethoxyethenyl)-6-methoxycarbonyl-2-(4-trifluoromethylphenyl)- -pyrimidine (compound 31-67)

##STR00190##

[0495] A solution of 4-amino-5-chloro-6-methoxycarbonyl-2-(4-trifluoromethylphenyl)-pyrimidine (prepared as described in example 5) (662 mg, 2.0 mmol), 1-ethoxy-1-tributylstannyl-ethene (0.8 ml, 2.4 mmol) and palladium tetrakis(triphenylphosphine) (462 mg, 0.40 mmol) in dimethylsulphoxide (14 ml) was heated at 170.degree. C. in a microwave reactor for 30 minutes. The reaction mixture was allowed to cool, potassium fluoride (saturated solution in methanol; 30 ml) added and the resulting mixture stirred for 17 hours at ambient temperature. The mixture was filtered through Celite.RTM., the solid washed with methanol and the filtrate concentrated under reduced pressure. The residue was extracted with ether and ethyl acetate and the combined organic extracts washed with brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure. The crude material was purified column chromatography on silica using hexane/ethyl acetate (4:1) as eluent to provide 4-amino-5-(1-ethoxyethenyl)-6-methoxycarbonyl-2-(4-trifluoromethylphenyl)- -pyrimidine as a pale yellow solid (651 mg, 89%). .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 8.50 (2H, d), 7.80 (2H, d), 5.60 (2H, br s), 4.50 (2H, dd), 3.90 (2H, q), 3.90 (3H, s), 1.40 (3H, t) ppm.

[0496] Further examples, prepared using this general method, are listed in Table 11 below.

TABLE-US-00019 TABLE 11 Compounds made according to the general method described in Example 18 above. Characteristic data is .sup.1H nmr data (400 MHz, CDCl.sub.3) .delta..sub.H ppm Compound Characteristic No. Name Structure data 33-67 4-Amino-2-(4-chloro- 3-dimethylamino-2- fluorophenyl)-5-(1- ethoxyethenyl)-6- methoxycarbonyl- pyrimidine ##STR00191## 7.60 (1H, t), 7.20 (1H, dd), 5.60 (2H, br s), 4.50 (2H, dd), 3.90 (3H, s), 3.90 (2H, q), 2.90 (6H, s), 1.40 (3H, t) 27-67 4-Amino-2-(4-chloro- 2-fluoro-3- methoxyphenyl)-5- (1-ethoxyethenyl)-6- methoxycarbonyl- pyrimidine ##STR00192## 7.60 (1H, t), 7.20 (1H, dd), 5.60 (2H, br s), 4.50 (2H, dd), 4.00 (3H, d), 3.90 (3H, s), 3.90 (2H, q), 1.40 (3H, t)

[0497] Also isolated from a reaction of this type was 4-amino-2-(4-[1-ethoxyethenyl]-2-fluoro-3-methoxy-phenyl)-6-methoxycarbon- yl-5-methylcarbonyl-pyrimidine (compound 66-53).

[0498] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 7.60 (1H, t), 7.50 (1H, dd), 5.70 (2H, br s), 4.50 (2H, dd), 4.00 (3H, d), 3.90 (3H, s), 3.90 (2H, q), 2.60 (3H, s), 1.40 (3H, t) ppm.

Example 19

Synthesis of 4-amino-6-methoxycarbonyl-5-methylcarbonyl-2-(4-trifluoromethylphenyl)-py- rimidine (compound 31-53)

##STR00193##

[0500] A solution of 4-amino-5-(1-ethoxyethenyl)-6-methoxycarbonyl-2-(4-trifluoromethylphenyl)- -pyrimidine (prepared as described in Example 18) (300 mg, 0.82 mmol) and hydrochloric acid (1M; 6 ml, 6 mmol) in tetrahydrofuran (12 ml) was stirred at ambient temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, extracted with ethyl acetate and the combined organic extracts washed with aqueous sodium hydrogen carbonate and brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure. The crude product was purified by column chromatography on silica using a gradient of hexane/ethyl acetate (100:0 to 4:1) as eluent to provide 4-amino-6-methoxycarbonyl-5-methylcarbonyl-2-(4-trifluoromethylphenyl)-py- rimidine as an off white solid (241 mg, 87%).

[0501] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 8.50 (2H, d), 7.70 (2H, d), 4.00 (3H, s), 3.48 (2H, br s), 2.50 (3H, s) ppm.

[0502] Further examples, prepared using this general method, are listed in Table 12 below.

TABLE-US-00020 TABLE 12 Compounds made according to the general method described in Example 19 above. Characteristic data is .sup.1H nmr data (400 MHz, CDCl.sub.3) .delta..sub.H ppm Compound Characteristic No. Name Structure data 33-53 4-Amino-2-(4-chloro- 3-dimethylamino-2- fluorophenyl)-6- methoxycarbonyl-5- methylcarbonyl- pyrimidine ##STR00194## 7.70 (1H, t), 7.20 (1H, dd), 4.00 (3H, s), 2.90 (6H, s), 2.50 (3H, s) (amine protons not observed) 27-53 4-Amino-2-(4-chloro- 2-fluoro-3-methoxy- phenyl)-6- methoxycarbonyl-5- methylcarbonyl- pyrimidine ##STR00195## 7.70 (1H, t), 7.20 (1H, dd), 4.10 (3H, s), 4.00 (3H, s), 2.50 (3H, s) (amine protons not observed) 65-53 4-Amino-2-(2-fluoro- 3-methoxy-4- methylcarbonyl- phenyl)-6- methoxycarbonyl-5- methylcarbonyl- pyrimidine ##STR00196## 7.70 (1H, t), 7.50 (1H, dd), 4.10 (3H, s), 4.00 (3H, s), 2.70 (3H, s), 2.50 (3H, s) (amine protons not observed)

Example 20

Synthesis of 4-amino-5-(1-hydroxyethyl)-6-hydroxymethyl-2-(4-trifluoromethylphenyl)-py- rimidine (compound 31-372)

##STR00197##

[0504] Sodium borohydride (11 mg, 0.30 mmol) was added to a stirred solution of 4-amino-6-methoxycarbonyl-5-methylcarbonyl-2-(4-trifluoromethylphenyl)-py- rimidine (prepared as described in example 19) (51 mg, 0.15 mmol) in methanol (2 ml). The reaction mixture was stirred at ambient temperature for 1 hour, then 1N hydrochloric acid (1 ml) was added and the mixture concentrated under reduced pressure and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure. The residue was purified using a FractionLynx automated hplc system to provide 4-amino-5-(1-hydroxyethyl)-6-hydroxymethyl-2-(4-trifluoromethylphenyl)-py- rimidine as a colourless oil (13 mg, 28%).

[0505] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 8.40 (2H, d), 7.70 (2H, d), 6.00 (2H, br s), 5.00 (1H, q), 4.80 (1H, br s), 4.60 (2H, q), 2.70 (1H, br s), 1.50 (3H, d) ppm.

Example 21

Synthesis of 4-amino-5-ethyl-6-methoxycarbonyl-2-(4-trifluoro-methylphenyl)-pyrimidine (compound 31-42)

##STR00198##

[0507] A solution of 4-amino-5-ethenyl-6-methoxycarbonyl-2-(4-trifluoromethylphenyl)-pyrimidin- e (prepared using the method described in example 8) (38 mg, 0.11 mmol) in methanol (10 ml) was reduced using a Thales H-cube reactor fitted with a 30 mm palladium on carbon cartridge. The reaction was performed at 30.degree. C. and 20 bar pressure at a flow rate of 1 ml/minute. The reaction solution was evaporated under reduced pressure to provide 4-amino-5-ethyl-6-methoxycarbonyl-2-(4-trifluoromethylphenyl)-pyrimidine (38 mg, 99%).

[0508] M.p. 123-124.degree. C.; .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 8.50 (2H, d), 7.70 (2H, d), 5.30 (2H, br s), 4.00 (3H, s), 2.70 (2H, q), 1.30 (3H, t) ppm.

[0509] Further compounds, prepared using this general method, are listed in Table 13 below.

TABLE-US-00021 TABLE 13 Compounds made according to the general method described in Example 21 above. Characteristic data provided is .sup.1H-nmr data (400 MHz, CDCl.sub.3) .delta..sub.H ppm Compound No. Name Structure Characteristic data 31-43 4-Amino-6- methoxycarbonyl- 5-propyl-2-(4- trifluoromethyl- phenyl)-pyrimidine ##STR00199## 8.50 (2H, d), 7.70 (2H, d), 5.20 (2H, br s), 4.00 (3H, s), 2.60 (2H, q), 1.70 (2H, septet), 1.10 (3H, t)

Example 22

Synthesis of 4-amino-2-(3-dimethylamino-4-ethenyl-2-fluorophenyl)-5-ethenyl-6-methoxyc- arbonylpyrimidine (compound 64-61)

##STR00200##

[0511] A mixture of 4-amino-2-(4-chloro-3-dimethylamino-2-fluorophenyl)-5-ethenyl-6-methoxyca- rbonylpyrimidine (prepared as described in example 8) (200 mg, 0.57 mmol), vinyl boronic acid pinacol ester (0.12 ml, 0.69 mmol), palladium acetate (6 mg, 0.029 mmol), tricyclohexylphosphine tetrafluoroborate (21 mg, 0.057 mmol), potassium phosphate (363 mg, 1.7 mmol), toluene (3.6 ml) and water (0.4 ml) was purged with nitrogen, then heated in a microwave reactor at 180.degree. C. for 30 minutes. The reaction mixture was allowed to cool, water added and the resulting mixture extracted with dichloromethane. The organic phase was washed with brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure. The residue was purified by chromatography on silica using hexane/ethyl acetate (first 8:2, then 6:4) as eluent to provide 4-amino-2-(3-dimethylamino-4-ethenyl-2-fluorophenyl)-5-ethenyl-6-methoxyc- arbonylpyrimidine as a yellow oil (95 mg, 49%).

[0512] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 7.60 (1H, t), 7.35 (1H, d), 7.20 (1H, dd), 6.80 (1H, dd), 5.70 (3H, m), 5.40 (2H, br s), 5.30 (1H, d), 3.90 (3H, s), 2.80 (6H, s) ppm.

Example 23

Synthesis of 4-chloro-2-fluoro-3-methoxybenzamidine

23.1 Preparation of 3-bromo-6-chloro-2-fluorophenol

##STR00201##

[0514] n-Butyllithium (2.1M in hexane; 68 ml, 149 mmol) was added dropwise to a stirred solution of diisopropylamine (15 g, 149 mmol) in anhydrous tetrahydrofuran (700 ml) at -78.degree. C. under a nitrogen atmosphere. Once the addition was complete the reaction mixture was allowed to warm to 0.degree. C., cooled to -78.degree. C. and a solution of 1-bromo-4-chloro-2-fluorobenzene (25 g, 119 mmol) in anhydrous tetrahydrofuran (60 ml) was added dropwise. The mixture was allowed to warm to -20.degree. C., cooled to -78.degree. C. and a solution of trimethylborate (15 g, 143 mmol) in anhydrous tetrahydrofuran (30 ml) added dropwise. The reaction mixture was allowed to warm to -20.degree. C. and stirred at that temperature for 30 minutes, then cooled to -78.degree. C. and peracetic acid (80 ml) added dropwise. The mixture was allowed to warm to ambient temperature and stirred overnight under nitrogen. Water (11) was added and the resulting mixture extracted with ethyl acetate (3.times.500 ml). The combined organic extracts were washed with water and brine, dried over sodium sulphate, filtered and evaporated under reduced pressure. The residue was purified by column chromatography on silica using 2% ethyl acetate in hexane as eluent to provide 3-bromo-6-chloro-2-fluorophenol (13.8 g, 51%).

23.2 Preparation of 1-bromo-4-chloro-2-fluoro-3-methoxybenzene

##STR00202##

[0516] Anhydrous potassium carbonate (17 g, 122 mmol) was added to a solution of 3-bromo-6-chloro-2-fluorophenol (13.8 g, 61 mmol) in anhydrous acetonitrile (100 ml). at ambient temperature. Methyl iodide (17 g, 122 mmol) was then added dropwise. The resulting mixture was heated at reflux for 2 hours, then cooled to ambient temperature and filtered through Celite.RTM., the solid being washed with acetonitrile. The filtrate was evaporated under reduced pressure, the residue dissolved in ethyl acetate (250 ml) and washed with water (100 ml). The aqueous phase was extracted with ethyl acetate (100 ml and the combined organic phases were washed with brine, dried over sodium sulphate, filtered and evaporated under reduced pressure. The crude product was purified by column chromatography on silica using hexane as eluent to provide 1-bromo-4-chloro-2-fluoro-3-methoxybenzene as a colourless oil, which solidified on storage at 5.degree. C. (11.4 g, 78%).

23.3 Preparation of 4-chloro-2-fluoro-3-methoxybenzonitrile

##STR00203##

[0518] Copper(I) cyanide (57 g, 0.64 mol) was added to a degassed solution of 1-bromo-4-chloro-2-fluoro-3-methoxybenzene (76 g, 0.32 mol) in anhydrous dimethylformamide (760 ml). The resulting mixture was again degassed and tetrakis(triphenylphosphine) palladium(0) (1.2 g) added. The reaction mixture was heated at 110.degree. C. under nitrogen for 24 hours, then allowed to cool to ambient temperature and water (2.5 l) added. The resulting mixture was stirred for 10 minutes, then filtered through Celite.RTM. and the solid washed with ethyl acetate (500 ml). The filtrate was separated into phases and the aqueous extracted with ethyl acetate (3.times.500 ml). The combined organic phases were washed with water and brine, dried over sodium sulphate, filtered and evaporated under reduced pressure. The crude product which was purified by column chromatography on silica using agradient of ethyl acetate (2-5%) in hexane as eluent to provide 4-chloro-2-fluoro-3-methoxybenzonitrile as a colourless solid (38 g, 65%).

23.4 Preparation of 4-chloro-2-fluoro-3-methoxybenzamidine

##STR00204##

[0520] n-Butyllithium (2.2M in hexane; 196 ml, 0.43 mol) was added dropwise to a solution of hexamethyldisilazane (72 g, 0.45 mol) in anhydrous diethyl ether (800 ml) at -15.degree. C. under a nitrogen atmosphere. The resulting solution was stirred at -15.degree. C. for 1 hour, then a solution of 4-chloro-2-fluoro-3-methoxybenzonitrile (40 g, 0.22 mol) in anhydrous diethyl ether (600 ml) was added dropwise. The reaction mixture was stirred at -15.degree. C. for 30 minutes, then allowed to warm to ambient temperature and stirring continued for 2 hours. The mixture was cooled to -10.degree. C., hydrochloric acid (3M; 360 ml) added dropwise and the resulting mixture stirred at 0.degree. C. for 45 minutes. The phases were separated and the aqueous layer washed with ethyl acetate (250 ml). The aqueous phase was cooled to 0.degree. C., basified by the addition of aqueous sodium hydroxide (3M) and extracted with ethyl acetate (3.times.300 ml). The combined organic extracts were dried over sodium sulphate, filtered and evaporated under reduced to provide 4-chloro-2-fluoro-3-methoxybenzamidine as a yellow solid (33 g, 75%).

Example 24

Synthesis of 4-chloro-6-ethoxycarbonyl-5-methyl-2-(4-trifluoromethylphenyl)-pyrimidine (compound 31-390)

24.1 Preparation of 6-ethoxycarbonyl-4-hydroxy-5-methyl-2-(4-trifluoromethylphenyl)-pyrimidin- e and 4,6-dihydroxy-6-ethoxycarbonyl-5-methyl-2-(4-trifluoromethylphenyl)-- 3,4-dihydropyrimidine

##STR00205##

[0522] A suspension of sodium ethoxide (940 mg, 13.8 mmol) in ethanol (4.5 ml) was added to a solution of 4-(trifluoromethyl)benzamidine hydrochloride dihydrate (2.79 g, 12.4 mmol) and diethyl oxalpropiolate (2.6 ml, 13.8 mmol) in ethanol (30 ml) and the resulting mixture stirred at ambient temperature for 18 hours. The reaction mixture was concentrated under reduced pressure, then dichloromethane was added and the solution dried over magnesium sulphate, filtered and evaporated under reduced pressure. The crude product was purified by chromatography on silica using hexane/ethyl acetate (3:2) as eluent to provide a mixture of 6-ethoxycarbonyl-4-hydroxy-5-methyl-2-(4-trifluoromethylphenyl)-pyrimidin- e and 4,6-dihydroxy-6-ethoxycarbonyl-5-methyl-2-(4-trifluoromethylphenyl)-- 3,4-dihydropyrimidine as a pale brown solid (2.21 g).

24.2 Preparation of 4-chloro-6-ethoxycarbonyl-5-methyl-2-(4-trifluoromethylphenyl)-pyrimidine (compound 31-390)

##STR00206##

[0524] Phosphorus oxychloride (5 ml) was added to a mixture of 6-ethoxycarbonyl-4-hydroxy-5-methyl-2-(4-trifluoromethylphenyl)-pyrimidin- e and 4,6-dihydroxy-6-ethoxycarbonyl-5-methyl-2-(4-trifluoromethylphenyl)-- 3,4-dihydropyrimidine (640 mg, 1.9 mmol) in a sealed vial. The resulting mixture was heated at 105.degree. C. for 3 hours, then cooled to ambient temperature and allowed to stand for 18 hours. The mixture was poured onto ice and solid sodium hydrogen carbonate added to bring the pH to 7. The resulting mixture was extracted with ethyl acetate and the combined organic extracts washed with brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure to provide 4-chloro-6-ethoxycarbonyl-5-methyl-2-(4-trifluoromethylphenyl)-pyrimidine as a brown oil (142 mg).

[0525] MH.sup.+ 345, 347.

Example 25

Synthesis of 4-dimethylamino-6-ethoxycarbonyl-5-methyl-2-(4-trifluoromethylphenyl)-pyr- imidine (compound 31-301)

##STR00207##

[0527] A solution of 4-chloro-6-ethoxycarbonyl-5-methyl-2-(4-trifluoromethylphenyl)-pyrimidine (prepared as described in example 24) (100 mg, 0.29 mmol), dimethylamine hydrochloride (47 mg, 0.58 mmol) and triethylamine (0.08 ml, 0.58 mmol) in dichloromethane (2 ml) was stirred at ambient temperature for 2.5 hours. Ethyl acetate was added and the resulting solution washed with brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure. A sub-sample of the residue was purified using a FractionLynx automated hplc system to provide 4-dimethylamino-6-ethoxycarbonyl-5-methyl-2-(4-trifluoromethylphenyl)-pyr- imidine as a yellow oil (7 mg)

[0528] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 8.50 (2H, d), 7.70 (2H, d), 4.50 (2H, q), 3.20 (6H, s), 2.40 (3H, s), 1.50 (3H, t) ppm.

Example 26

Synthesis of 5-chloro-2-cyclopropyl-4-methoxy-6-methoxycarbonyl-pyrimidine

##STR00208##

[0530] Triethylamine (1 ml, 2.5 mmol) was added to a stirred solution of 2-cyclopropyl-4,5-dichloro-6-methoxycarbonylpyrimidine (prepared as described in example 1) (500 mg, 2.0 mmol) in methanol (10 ml). The mixture was heated at 45.degree. C. for 14 hours, allowed to stand at ambient temperature for 72 hours, and then evaporated under reduced pressure. The residue was dissolved in ethyl acetate and the resulting solution washed with water and brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure to provide 5-chloro-2-cyclopropyl-4-methoxy-6-methoxycarbonyl-pyrimidine as a white solid (400 mg, 81%).

[0531] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 4.03 (3H, s), 4.00 (3H, s), 2.20 (1H, m), 1.12 (2H, m), 1.08 (2H, m) ppm.

[0532] Further examples, prepared using this general method, are listed in Table 14 below.

TABLE-US-00022 TABLE 14 Compounds made according to the general method described in Example 26 above. Melting point Name Structure (.degree. C.) 5-Chloro-2-(4- chloro-2-fluoro- 3-methoxy- phenyl)-4- methoxy-6- methoxy- carbonyl- pyrimidine ##STR00209## 143-145

Example 27

Synthesis of 2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-ethenyl-4-methoxy-6-methoxycarbon- yl-pyrimidine (compound 27-398)

##STR00210##

[0534] A mixture of vinyl boronic acid pinacol ester (0.1 ml, 0.58 mmol), 5-chloro-2-(4-chloro-2-fluoro-3-methoxyphenyl)-4-methoxy-6-methoxycarbony- lpyrimidine (prepared as described in example 26) (200 mg, 0.55 mmol), caesium fluoride (168 mg, 1.1 mmol), [1,1'-bis(diphenylphosphino)-ferrocene] dichloropalladium (II) complex with dichloromethane (1:1) (46 mg, 0.056 mmol), dimethoxyethane (2 ml) and water (2 ml) was heated in a microwave reactor at 150.degree. C. for 20 minutes, then allowed to cool. Ethyl acetate was added and the solution washed with brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure to leave a brown gum, which was purified by chromatography on silica using hexane/ethyl acetate (9:1 then 4:1) as eluent to provide 2-(4-chloro-2-fluoro-3-methoxyphenyl)-5-ethenyl-4-methoxy-6-methoxycarbon- yl-pyrimidine as a white solid (115 mg, 59%).

[0535] M.p. 107-108.degree. C.; .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 7.82 (1H, t), 7.24 (1H, d), 6.82 (1H, q), 6.06 (1H, d), 5.63 (1H, d), 4.17 (3H, s), 4.04 (6H, s), 3.97 (3H, s) ppm.

[0536] Further examples, prepared using this general method, are listed in Table 15 below.

TABLE-US-00023 TABLE 15 Compounds made according to the general method described in Example27 above. Characteristic data is .sup.1H nmr data (400 MHz, CDCl.sub.3) .delta..sub.H ppm Com- pound Characteristic No. Name Structure data 2-398 2-Cyclopropyl- 5-ethenyl-4- methoxy-6- methoxy- carbonyl- pyrimidine ##STR00211## 6.71 (1H, dd), 5.89 (1H, d), 5.50 (1H, d), 4.00 (3H, s), 3.95 (3H, s), 2.20 (1H, m), 1.14 (2H, m), 1.03 (2H, m)

Example 28

Synthesis of 2-cyclopropyl-5-ethenyl-6-methoxycarbonyl-4-methylthio-pyrimidine (compound 2-400)

28.1 Preparation of 5-chloro-2-cyclopropyl-6-methoxycarbonyl-4-methylthio-pyrimidine

##STR00212##

[0538] Sodium methanethiolate (1.0 g, 14 mmol) was added portionwise to a stirred solution of 2-cyclopropyl-4,5-dichloro-6-methoxycarbonylpyrimidine (prepared as described in example 1) (2.46 g, 10 mmol) in methanol (50 ml). The resulting mixture was stirred at ambient temperature for 1.5 hours, then evaporated under reduced pressure. The residue was partitioned between ethyl acetate and water and the organic phase washed with water and brine, dried over magnesium sulphate, filtered and evaporated to provide 5-chloro-2-cyclopropyl-6-methoxycarbonyl-4-methylthio-pyrimidine as a white solid (2.1 g, 80%).

[0539] M.p. 74-75.degree. C.; .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 4.00 (3H, s), 2.50 (3H, s), 2.24 (1H, m), 1.17 (2H, m), 1.10 (2H, m) ppm.

28.2 Preparation of 2-cyclopropyl-5-ethenyl-6-methoxycarbonyl-4-methylthio-pyrimidine (compound 2-400)

##STR00213##

[0541] A mixture of vinyl boronic acid pinacol ester (0.4 ml, 2 mmol), 5-chloro-2-cyclopropyl-6-methoxycarbonyl-4-methylthio-pyrimidine (258 mg, 1.0 mmol), caesium fluoride (0.6 g, 4 mmol), [1,1'-bis(diphenylphosphino)-ferrocene] dichloropalladium (II) complex with dichloromethane (1:1) (200 mg, 0.25 mmol), dimethoxyethane (3 ml) and water (2 ml) was heated in a microwave reactor at 140.degree. C. for 1 hour, then allowed to cool. Ethyl acetate was added and the solution washed with water and brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure to leave a brown oil, which was purified by chromatography on silica using hexane/ethyl acetate (4:1) as eluent to provide 2-cyclopropyl-5-ethenyl-6-methoxycarbonyl-4-methylthio-pyrimidine as a colourless gum (150 mg, 60%).

[0542] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 6.68 (1H, m), 5.55 (2H, m), 3.90 (3H, s), 2.50 (3H, s), 2.23 (1H, m), 1.20 (2H, m), 1.08 (2H, m) ppm.

Example 29

Synthesis of (i) 2-cyclopropyl-5-ethenyl-6-methoxycarbonyl-4-methylsulphinyl-pyrimidine (compound 2-401) and (ii) 2-cyclopropyl-5-ethenyl-6-methoxycarbonyl-4-methylsulphonyl-pyrimidine (compound 2-402)

##STR00214##

[0544] Peracetic acid (32% solution in dilute acetic acid; 0.25 ml, 1.1 mmol) was added dropwise to a stirred solution of 2-cyclopropyl-5-ethenyl-6-methoxycarbonyl-4-methylthio-pyrimidine (prepared as described in example 28) (125 mg, 0.5 mmol) in dichloromethane (5 ml) at 0.degree. C. The reaction mixture was stirred at ambient temperature for 1 hour, then further dichloromethane added and the resulting solution washed with water and brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure to leave a yellow gum. This was purified by chromatography on silica using hexane/ethyl acetate (4:1) as eluent to provide 2-cyclopropyl-5-ethenyl-6-methoxycarbonyl-4-methylsulphinyl-pyrimidine as a white solid (40 mg, 30%).

[0545] M.p. 74-75.degree. C.; .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 7.02 (1H, dd), 5.67 (1H, d), 5.50 (1H, d), 3.95 (3H, s), 2.88 (3H, s), 2.42 (1H, m), 1.27 (2H, m), 1.10 (2H, m) ppm.

[0546] Also isolated, as a yellow solid, was 2-cyclopropyl-5-ethenyl-6-methoxycarbonyl-4-methylsulphonyl-pyrimidine (10 mg, 7%).

[0547] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 7.18 (1H, dd), 5.65 (1H, d), 5.58 (1H, d), 3.94 (3H, s), 3.33 (3H, s), 2.38 (1H, m), 1.20 (4H, m) ppm.

Example 30

Synthesis of 4-azido-2-cyclopropyl-5-ethenyl-6-methoxycarbonyl-pyrimidine (compound 2-399)

##STR00215##

[0549] m-Chloroperbenzoic acid (516 mg, 3.0 mmol) was added portionwise to a stirred solution of 2-cyclopropyl-5-ethenyl-6-methoxycarbonyl-4-methylthio-pyrimidine (prepared as described in example 28) (250 mg, 1.0 mmol) in dichloromethane (10 ml) at 0.degree. C. The reaction mixture was allowed to stand at ambient temperature for 16 hours, then further dichloromethane added and the resulting solution washed with water and brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure to leave a gum. This was dissolved in methanol (10 ml) and sodium azide (500 mg, 7.7 mmol) added portionwise. The reaction mixture was then allowed to stand at ambient temperature for 64 hours, filtered and the filtrate evaporated under reduced pressure. The residue was purified by chromatography on silica using hexane/ethyl acetate (4:1) as eluent to provide 4-azido-2-cyclopropyl-5-ethenyl-6-methoxycarbonylpyrimidine as a white solid (65 mg, 27%).

[0550] M.p. 120-130.degree. C. (decomp.); .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 7.18 (1H, dd), 5.65 (1H, d), 5.58 (1H, d), 3.94 (3H, s), 2.38 (1H, m), 1.60 (2H, m), 1.46 (2H, m) ppm.

Example 31

Synthesis of (i) 2-cyclopropyl-4-hydroxy-6-methoxycarbonyl-methoxy-5-methylpyrimidine and (ii) 4,6-bis(methoxycarbonyl-methoxy)-2-cyclopropyl-5-methylpyrimidine (compound 2-384)

##STR00216##

[0552] A mixture of 2-cyclopropyl-4,6-dihydroxy-5-methylpyrimidine (1.6 g, 9.6 mmol), methyl bromoacetate (1.5 g, 9.8 mmol), potassium carbonate (1.4 g, 10 mmol) and dimethylformamide (7.5 ml) was heated at 90.degree. C. for 6 hours, then allowed to cool and stood at ambient temperature for 65 hours. Water was added and the resulting precipitate washed with ether and dried to provide a white solid. This was washed with ethyl acetate to provide 2-cyclopropyl-4-hydroxy-6-methoxycarbonylmethoxy-5-methylpyrimidi- ne as a white solid (450 mg, 19%).

[0553] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 13.80 (1H, br s), 4.70 (2H, s), 3.70 (3H, s), 1.90 (4H, m), 1.05 (4H, m) ppm.

[0554] The combined ethyl acetate washings were evaporated under reduced pressure and the residue purified by column chromatography on silica using ethyl acetate as eluent to provide 4,6-bis(methoxycarbonylmethoxy) 2-cyclopropyl-5-methylpyrimidine as a solid (450 mg, 15%).

[0555] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 4.80 (4H, br s), 3.75 (6H, s), 2.10 (3H, s), 1.95 (1H, m), 0.90 (4H, m) ppm.

[0556] Further compounds, prepared using this general method, are listed in Table 16 below.

TABLE-US-00024 TABLE 16 Compounds made according to the general method described in Example 31 above. Characteristic data provided is .sup.1H-nmr data (400 MHz, CDCl.sub.3) .delta..sub.H ppm Com- Character- pound istic No. Name Structure data 2-389 4,6-bis(t- butoxy- carbonyl- methoxy)- 2-cyclo- propyl- 5-methyl- pyrimidine ##STR00217## 4.85 (2H, s), 4.60 (2H, s), 1.90 (3H, s), 1.65 (1H, m), 1.45 (18H, s), 1.10 (2H, m), 0.90 (2H, m)

Example 32

Synthesis of 4-chloro-2-cyclopropyl-6-methoxycarbonylmethoxy-5-methylpyrimidine (compound 2-376)

##STR00218##

[0558] A stirred suspension of 2-cyclopropyl-4-hydroxy-6-methoxycarbonylmethoxy-5-methylpyrimidine (prepared as described in example 31) (450 mg, 1.9 mmol) in phosphorus oxychloride (3 ml) was heated at 120.degree. C. for 5 hours. The reaction mixture was allowed to cool and evaporated under reduced pressure. The residue was dissolved in dichloromethane and the solution washed with saturated aqueous sodium bicarbonate, dried over magnesium sulphate, filtered and evaporated under reduced pressure. The residue was purified by column chromatography on silica using diethyl ether as eluent to provide 4-chloro-2-cyclopropyl-6-methoxycarbonylmethoxy-5-methylpyrimidin- e as a solid (350 mg, 70%).

[0559] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 4.85 (2H, s), 3.75 (3H, s), 2.20 (3H, s), 2.10 (1H, m), 1.00 (4H, m) ppm.

Example 33

Synthesis of 4-amino-2-cyclopropyl-6-methoxycarbonylmethoxy-5-methylpyrimidine (compound 2-362)

33.1 Preparation of 4-azido-2-cyclopropyl-6-methoxycarbonylmethoxy-5-methylpyrimidine (compound 2-388)

##STR00219##

[0561] A stirred solution of 4-chloro-2-cyclopropyl-6-methoxycarbonylmethoxy-5-methylpyrimidine (prepared as described in example 32) (256 mg, 1.0 mmol) and sodium azide (100 mg, 1.5 mmol) in dimethylformamide (10 ml) was heated at 90.degree. C. for 3 hours. The reaction mixture was allowed to cool and added to water. Ether was added, the mixture stirred for 30 minutes, then the phases separated. The organic phase was dried over magnesium sulphate, filtered and evaporated under reduced pressure to provide 4-azido-2-cyclopropyl-6-methoxycarbonylmethoxy-5-methylpyrimidine as an oil (200 mg, 76%).

[0562] MH.sup.+: 264.

33.2 Preparation of 4-amino-2-cyclopropyl-6-methoxycarbonylmethoxy-5-methylpyrimidine (compound 2-362)

##STR00220##

[0564] A mixture of 4-azido-2-cyclopropyl-6-methoxycarbonylmethoxy-5-methylpyrimidine (200 mg, 0.76 mmol) and palladium (5% on carbon; catalytic) in methanol (20 ml) was stirred under an atmosphere of hydrogen (4 bar) for 5 minutes. The reaction mixture was allowed to cool and added to water. Ether was added, the mixture stirred for 30 minutes, then the phases separated. The organic phase was dried over magnesium sulphate, filtered and evaporated under reduced pressure to provide 4-amino-2-cyclopropyl-6-methoxycarbonylmethoxy-5-methylpyrimidine.

[0565] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 4.85 (2H, s), 3.75 (3H, s), 2.20 (3H, s), 2.10 (1H, m), 1.00 (4H, m) ppm (amino protons not observed).

Example 34

Synthesis of (4-chloro-2-cyclopropyl-5-methyl-pyrimidin-6-yloxy)-acetic acid (compound 2-375)

##STR00221##

[0567] A solution of 4-chloro-2-cyclopropyl-6-methoxycarbonylmethoxy-5-methylpyrimidine (prepared as described in example 32) (256 mg, 1.0 mmol) and ammonia (7M in methanol; 0.6 ml, 4 mmol) in methanol (2.5 ml) was heated in a microwave reactor at 120.degree. C. for 20 minutes, then cooled and evaporated under reduced pressure. The residue was triturated with diethyl ether to provide (4-chloro-2-cyclopropyl-5-methyl-pyrimidin-6-yloxy)-acetic acid as a white solid (220 mg, 91%).

[0568] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 12.0 (1H, br s), 4.81 (2H, s), 2.20 (3H, s), 2.10 (1H, m), 1.10 (4H, m) ppm.

Example 35

synthesis of 4-amino-5-ethenyl-6-methoxycarbonylmethoxy-2-methylthio-pyrimidine (compound 2-366)

35.1 Preparation of 4-chloro-6-hydroxy-5-iodo-2-methylthio-pyrimidine

##STR00222##

[0570] N-Iodosuccinimide (8.1 g, 36 mmol) was added to a stirred solution of 2-chloro-6-hydroxy-2-methylthiopyrimidine (5.28 g, 30 mmol) in methanol (100 ml) and the resulting mixture stirred at ambient temperature for 1 hour. The reaction mixture was filtered and the solid washed with diethyl ether to provide 4-chloro-6-hydroxy-5-iodo-2-methylthiopyrimidine as a white solid (8.0 g, 88%).

[0571] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 2.50 (3H, s) ppm (hydroxy proton not observed).

35.2 Preparation of 4,6-dichloro-5-iodo-2-methylthio-pyrimidine

##STR00223##

[0573] A suspension of 4-chloro-6-hydroxy-5-iodo-2-methylthiopyrimidine (906 mg, 3.0 mmol) in phosphorus oxychloride (6 ml, 60 mmol) was heated at reflux for 3 hours, then allowed to cool and poured into iced water. The mixture was filtered and the solid purified by chromatography on silica using hexane/ethyl acetate (19:1) as eluent to provide 4,6-dichloro-5-iodo-2-methylthio-pyrimidine as a white solid (700 mg, 73%).

[0574] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 2.50 (3H, s) ppm.

35.3 Preparation of 4-amino-6-chloro-5-iodo-2-methylthio-pyrimidine

##STR00224##

[0576] A solution of 4,6-dichloro-5-iodo-2-methylthio-pyrimidine (320 mg, 1.0 mmol) and ammonia (7M in methanol; 0.15 ml, 1.1 mmol) in methanol (2.5 ml) was heated in a microwave reactor at 120.degree. C. for 20 minutes, then cooled to 0.degree. C. The solid was filtered and washed with hexane to provide 4-amino-6-chloro-5-iodo-2-methylthio-pyrimidine as a white solid (210 mg, 70%).

[0577] .sup.1H nmr (400 MHz, d.sub.6-DMSO) .delta..sub.F, 7.20 (2H, br s), 2.50 (3H, s) ppm.

35.4 Preparation of 4-amino-5-iodo-6-methoxycarbonylmethoxy-2-methylthio-pyrimidine

##STR00225##

[0579] Sodium hydride (50% in mineral oil; 72 mg, 1.5 mmol) was added to a stirred solution of methyl glycolate (99 mg, 1.1 mmol) in tetrahydrofuran (2 ml). After stirring for 10 minutes, a solution of 4-amino-6-chloro-5-iodo-2-methylthio-pyrimidine (301 mg, 1.0 mmol) in tetrahydrofuran was added and the reaction mixture heated at reflux for 2 hours. After cooling, saturated aqueous ammonium chloride was added and the resulting mixture extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure. The residue was purified by chromatography on silica, using a gradient of ethyl acetate in hexane (0-20%) as eluent to provide 4-amino-5-iodo-6-methoxycarbonylmethoxy-2-methylthio-pyrimidine as a yellow solid (130 mg, 36%).

[0580] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 5.30 (2H, br s), 4.88 (2H, s), 3.75 (3H, s), 2.50 (3H, s) ppm.

35.5 Preparation of 4-amino-5-ethenyl-6-methoxycarbonylmethoxy-2-methylthio-pyrimidine (compound 2-366)

##STR00226##

[0582] A mixture of vinyl boronic acid pinacol ester (0.067 ml, 0.375 mmol), 4-amino-5-iodo-6-methoxycarbonylmethoxy-2-methylthio-pyrimidine (89 mg, 0.25 mmol), caesium fluoride (76 mg, 0.50 mmol), [1,1'-bis(diphenylphosphino)-ferrocene] dichloropalladium (II) complex with dichloromethane (1:1) (20 mg, 0.025 mmol), dimethoxyethane (1.5 ml) and water (1.5 ml) was heated in a microwave reactor at 150.degree. C. for 20 minutes, then allowed to cool. Dichloromethane was added and the solution washed with brine, dried over magnesium sulphate, filtered and evaporated under reduced pressure. The residue was purified by chromatography on silica using hexane/ethyl acetate (4:1) as eluent to provide 4-amino-5-ethenyl-6-methoxycarbonylmethoxy-2-methylthio-pyrimidin- e as a brown solid (43 mg, 67%).

[0583] .sup.1H nmr (400 MHz, CDCl.sub.3) .delta..sub.H 6.60 (1H, m), 5.65 (1H, d), 5.50 (1H, d), 5.10 (2H, br s), 4.82 (2H, s), 3.72 (3H, s), 2.40 (3H, s) ppm.

Example 36

Pre-Emergence Biological Efficacy

[0584] Seeds of Alopecurus myosuroides (ALOMY), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG), Solanum nigrum (SOLNI), Amaranthus retoflexus (AMARE) and Ipomea hederaceae (IPOHE) were sown in standard soil in pots. After cultivation for one day under controlled conditions in a glasshouse (at 24/16.degree. C., day/night; 14 hours light; 65% humidity), the plants were sprayed with an aqueous spray solution derived from the formulation of the technical active ingredient in acetone/water (50:50) solution containing 0.5% Tween 20 (polyoxyethylene sorbitan monolaurate, CAS RN 9005-64-5) to give a final dose of 250 or 1000 g/ha of test compound.

[0585] The test plants were then grown under controlled conditions in the glasshouse (at 24/16.degree. C., day/night; 14 hours light; 65% humidity) and watered twice daily. After 13 days the test was evaluated (100=total damage to plant; 0=no damage to plant). Results are shown below in Table B1.

TABLE-US-00025 TABLE B1 Percentage damage caused to weed species by compounds of the invention when applied pre-emergence. Compound Species Number Dose (g/ha) SOLNI AMARE IPOHE SETFA ALOMY ECHCG 2-41 1,000 50 70 60 30 20 20 2-61 1,000 100 100 100 20 40 80 2-62 (E) 1,000 70 40 30 0 10 10 2-62 (Z) 1,000 100 90 100 20 20 10 2-64 1,000 80 100 100 20 20 0 2-65 250 0 0 0 0 0 0 2-66 1,000 0 -- 0 0 0 0 2-69 1,000 90 100 70 0 10 0 2-77 250 0 0 0 0 0 0 2-78 1,000 90 90 100 10 20 30 2-221 1,000 60 60 70 0 30 0 2-225 1,000 0 40 20 0 0 0 2-362 1,000 10 40 30 40 40 10 2-366 1,000 0 0 0 0 0 0 2-375 1,000 0 0 20 0 0 0 2-376 1,000 0 30 0 0 0 0 2-389 1,000 0 20 0 0 0 0 2-398 1,000 90 90 100 0 0 0 2-399 1,000 0 0 0 0 0 0 2-400 1,000 100 90 60 0 0 0 2-401 1,000 10 70 70 0 0 0 2-402 1,000 0 0 0 0 0 0 5-41 1,000 30 100 10 30 20 30 5-61 1,000 90 100 90 60 60 60 6-61 1,000 90 100 80 30 70 50 9-61 1,000 70 90 10 0 0 30 14-61 1,000 40 60 10 10 10 20 15-61 1,000 100 100 100 70 80 70 19-61 1,000 100 100 100 30 50 70 26-61 1,000 80 100 20 0 0 0 27-21 1,000 100 100 100 100 90 100 27-41 1,000 80 50 90 10 30 20 27-53 1,000 100 90 100 10 20 20 27-58 1,000 0 -- 10 0 0 0 27-61 1,000 100 100 90 90 90 90 27-62 (E) 1,000 80 50 90 80 90 90 27-62 (Z) 1,000 100 100 100 80 80 90 27-63 1,000 100 100 100 50 50 80 27-67 1,000 100 30 40 10 20 20 27-69 1,000 100 100 30 60 40 30 27-398 1,000 0 0 0 0 0 0 30-61 1,000 20 0 0 0 0 0 31-372 1,000 0 0 0 0 0 0 31-42 1,000 0 0 0 0 0 0 31-53 1,000 100 100 90 90 80 90 31-61 1,000 0 10 0 0 0 0 31-62 1,000 0 20 0 0 0 0 31-63 1,000 0 0 0 0 0 0 31-64 1,000 0 0 0 0 0 0 31-67 1,000 0 0 0 0 0 0 33-21 1,000 100 100 80 100 90 100 33-41 1,000 30 20 0 30 10 10 33-53 1,000 0 0 0 0 0 0 33-58 1,000 0 0 0 0 0 0 33-61 1,000 30 50 40 10 0 0 33-62 (E) 1,000 80 100 0 80 70 90 33-62 (Z) 1,000 60 70 20 30 30 30 33-64 1,000 0 0 0 0 0 0 33-67 1,000 0 0 10 0 0 0 33-101 1,000 90 100 30 90 60 90 33-306 1,000 80 40 0 20 20 20 33-316 1,000 80 90 10 70 60 90 33-326 1,000 60 60 10 20 20 40 33-336 1,000 80 100 20 80 70 90 33-391 1,000 100 100 20 90 70 100 33-392 1,000 80 100 0 90 70 100 33-393 1,000 20 20 0 0 0 0 33-394 1,000 40 40 0 30 20 30 33-395 1,000 100 100 30 80 60 90 33-396 1,000 90 100 50 80 70 90 33-397 1,000 100 100 50 90 80 100 36-61 1,000 100 100 100 80 70 90 41-61 1,000 0 100 40 10 20 10 42-61 1,000 20 60 0 20 10 10 43-61 1,000 70 60 10 50 30 70 44-61 1,000 40 50 10 30 20 40 45-61 1,000 40 100 0 50 50 40 47-61 1,000 0 0 0 0 0 0 60-41 1,000 40 0 10 10 20 10 61-61 1,000 30 0 0 0 0 0 62-61 1,000 100 100 100 0 0 0 63-61 1,000 0 0 0 0 0 0 64-61 1,000 10 30 0 10 10 10 65-53 1,000 0 0 20 0 0 0 66-53 1,000 20 10 30 0 0 0 67-61 1,000 70 100 50 30 30 30 68-61 250 30 10 0 0 0 0 69-61 1,000 0 0 0 0 0 0 70-61 1,000 100 100 80 70 80 90 71-61 1,000 40 0 0 0 10 20 72-61 1,000 50 60 70 0 0 0 73-61 1,000 0 0 0 0 0 0

Example 37

Post-Emergence Biological Efficacy

[0586] Seeds of Alopecurus myosuroides (ALOMY), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG), Solanum nigrum (SOLNI), Amaranthus retoflexus (AMARE) and Ipomea hederaceae (IPOHE) were sown in standard soil in pots. After cultivation for 8 days under controlled conditions in a glasshouse (at 24/16.degree. C., day/night; 14 hours light; 65% humidity), the plants were sprayed with an aqueous spray solution derived from the formulation of the technical active ingredient in acetone/water (50:50) solution containing 0.5% Tween 20 (polyoxyethylene sorbitan monolaurate, CAS RN 9005-64-5) to give a final dose of 250 or 1000 g/ha of test compound.

[0587] The test plants were then grown on under controlled conditions in a glasshouse (at 24/16.degree. C., day/night; 14 hours light; 65% humidity) and watered twice daily. After 13 days the test was evaluated (100=total damage to plant; 0=no damage to plant). Results are shown below in Table B2.

TABLE-US-00026 TABLE B2 Percentage damage caused to weed species by compounds of the invention when applied post-emergence Compound Species Number Dose (g/ha) SOLNI AMARE IPOHE SETFA ALOMY ECHCG 2-41 1,000 90 100 100 80 40 60 2-61 1,000 100 100 100 80 40 60 2-62 (E) 1,000 70 40 50 20 10 10 2-62 (Z) 1,000 70 70 100 30 10 10 2-64 1,000 80 60 70 30 10 40 2-65 250 40 20 40 0 0 0 2-66 1,000 60 50 40 10 0 0 2-69 1,000 80 20 70 10 10 0 2-77 250 40 30 70 0 0 0 2-78 1,000 100 100 100 60 30 60 2-221 1,000 80 100 80 60 20 70 2-225 1,000 50 40 30 0 0 0 2-362 1,000 80 80 80 70 40 60 2-366 1,000 20 0 0 0 0 0 2-375 1,000 10 10 20 0 0 0 2-376 1,000 30 20 50 20 0 0 2-389 1,000 30 0 20 0 0 0 2-398 1,000 80 90 90 0 0 0 2-399 1,000 20 20 20 0 0 0 2-400 1,000 100 80 60 0 0 0 2-401 1,000 80 70 70 0 0 0 2-402 1,000 20 0 50 0 0 0 5-41 1,000 70 100 40 30 30 20 5-61 1,000 100 100 100 100 80 90 6-61 1,000 90 100 70 30 60 50 9-61 1,000 90 100 70 0 20 20 14-61 1,000 80 10 40 0 0 0 15-61 1,000 100 100 80 70 90 70 19-61 1,000 100 100 100 40 40 60 26-61 1,000 80 100 70 0 50 60 27-21 1,000 90 100 90 100 90 90 27-41 1,000 80 100 60 80 30 50 27-53 1,000 90 100 60 40 30 30 27-58 1,000 80 90 60 40 10 20 27-61 1,000 80 100 80 100 90 90 27-62 (E) 1,000 100 100 90 100 90 100 27-62 (Z) 1,000 80 100 100 90 70 80 27-63 1,000 90 100 90 90 60 70 27-67 1,000 80 40 60 10 0 10 27-69 1,000 80 90 40 40 40 10 27-398 1,000 20 0 40 0 0 0 30-61 1,000 80 10 10 0 0 0 31-42 1,000 10 0 0 0 0 0 31-53 1,000 100 100 90 100 90 100 31-61 1,000 70 70 10 0 20 0 31-62 1,000 50 30 50 10 0 0 31-63 1,000 50 40 40 0 0 0 31-64 1,000 60 40 60 20 0 0 31-67 1,000 80 50 80 0 0 0 31-372 1,000 30 20 30 30 10 10 33-21 1,000 90 100 70 100 90 100 33-41 1,000 70 100 10 70 30 50 33-53 1,000 50 100 40 20 10 20 33-58 1,000 10 10 0 60 10 10 33-61 1,000 80 70 90 30 20 20 33-62 (Z) 1,000 80 100 40 80 80 80 33-62 (Z) 1,000 80 100 30 70 60 70 33-64 1,000 20 10 10 0 0 0 33-67 1,000 40 10 20 0 0 0 33-101 1,000 90 100 60 80 80 90 33-306 1,000 100 100 30 70 40 70 33-316 1,000 90 100 40 90 70 100 33-326 1,000 90 100 50 40 20 80 33-336 1,000 90 100 40 90 90 90 33-391 1,000 80 100 80 90 70 90 33-392 1,000 90 100 80 60 70 80 33-393 1,000 70 70 70 0 0 20 33-394 1,000 80 100 30 50 30 60 33-395 1,000 100 100 30 100 70 100 33-396 1,000 90 100 60 90 70 100 33-397 1,000 90 100 80 90 80 90 36-61 1,000 80 100 90 80 70 90 41-61 1,000 90 100 60 10 20 10 42-61 1,000 30 100 10 40 30 30 43-61 1,000 70 20 10 20 30 30 44-61 1,000 90 100 30 60 40 50 45-61 1,000 70 100 30 50 50 40 47-61 1,000 70 100 10 10 10 10 60-41 1,000 100 100 40 10 40 30 61-61 1,000 20 10 0 0 0 0 62-61 1,000 90 100 90 10 0 0 63-61 1,000 20 0 20 0 0 0 64-61 1,000 60 100 10 30 10 10 65-53 1,000 70 20 50 10 0 10 66-53 1,000 60 20 30 10 0 0 67-61 1,000 90 100 60 10 20 40 68-61 250 80 30 40 0 0 0 69-61 1,000 20 0 30 0 0 0 70-61 1,000 90 100 80 40 100 100 71-61 1,000 60 20 40 0 0 30 72-61 1,000 60 10 50 0 10 0 73-61 1,000 30 20 0 0 0 0

Claims

1. A compound of formula (I) ##STR00227## or salt or N-oxide thereof, wherein: A is halogen, optionally substituted alkylthio, optionally substituted alkyl, optionally substituted alkenyl or an optionally substituted 3-8 membered carbocyclic ring; X is azido, halogen, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkylsulphinyl, optionally substituted alkylsulphonyl or NR.sup.5R.sup.6; R.sup.5 is hydrogen, C.sub.2-4 alkenyl, SO.sub.2R.sup.ss, C(O)R.sup.uu or optionally substituted C.sub.1-4 alkyl; R.sup.6 is hydrogen, C.sub.2-4 alkenyl or optionally substituted C.sub.1-4; each R.sup.ss is independently C.sub.1-4 alkyl or phenyl optionally substituted by 1-3 groups R.sup.zz; each R.sup.uu is independently C.sub.1-4 alkyl, phenyl optionally substituted by 1-3 groups R.sup.zz, C.sub.1-4 alkoxy, or NR.sup.acR.sup.ad; each R.sup.zz is independently halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, or C.sub.1-4 alkylsulphonyl; R.sup.ac and R.sup.ad are each independently hydrogen or C.sub.1-4 alkyl; or R.sup.5 and R.sup.6 together form a group .dbd.C(R.sup.i)OR.sup.j, .dbd.C(R.sup.k)SR.sup.l, .dbd.C(R.sup.m)NR.sup.nR.sup.o wherein R.sup.i is hydrogen, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, phenyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, or NR.sup.acR.sup.ad wherein R.sup.ac and R.sup.ad are as defined above, R.sup.j and R.sup.l are each independently C.sub.1-4 alkyl, R.sup.k is hydrogen, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, phenyl, C.sub.1-4 alkylthio, or NR.sup.acR.sup.ad wherein R.sup.ac and R.sup.ad are as defined above, R.sup.m is hydrogen, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, phenyl, or NR.sup.acR.sup.ad wherein R.sup.ac and R.sup.ad are as defined above, and R.sup.n and R.sup.o are each independently hydrogen or C.sub.1-4alkyl; Y is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, or optionally substituted alkynyl; and, Z is O.sub.m--(CHR.sup.w).sub.n--C(O)R.sup.cb, wherein m is an integer of 0 or 1, n is an integer of 0 or 1 and n.gtoreq.m, R.sup.w is hydrogen or C.sub.1-4 alkyl R.sup.cb is hydroxy, optionally substituted alkylthio, NH.sub.2, or OR.sup.co, R.sup.co is C.sub.1-20 alkyl optionally substituted by 1-3 groups R.sup.cq, or C.sub.1-20 haloalkyl optionally substituted by 1-3 groups R.sup.cq; each R.sup.cq is independently C.sub.1-6 alkoxy, phenyl optionally substituted by 1-3 groups R.sup.cr, or heteroaryl optionally substituted by 1-2 groups R.sup.cs; each R.sup.cr and each R.sup.cs are independently halogen, cyano, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.2-6 alkoxyalkyl, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, C.sub.1-4alkylsulphonyl, or C.sub.1-4 alkoxycarbonyl; provided that: i) when Y is C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.2-4 alkoxyalkyl, C.sub.2-4 alkylthioalkyl, C.sub.2-4 alkenyl, C.sub.2-4 haloalkenyl, C.sub.2-4 alkoxyalkenyl, C.sub.2-4 thioalkylalkenyl, C.sub.2-4 alkynyl, C.sub.2-4 haloalkynyl, C.sub.2-4 alkylcarbonyl or C.sub.2-4 haloalkylcarbonyl; X is NR.sup.5R.sup.6; R.sup.5 is H, C.sub.1-4 alkyl, C.sub.3-4 alkenyl, C.sub.1-4 alkylsulfonyl or C.sub.1-4 acyl; R.sup.6 is H, C.sub.1-4 alkyl or C.sub.3-4 alkenyl; A is C1-C6 alkyl, cyclopropyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl or a group of the formula ##STR00228## W.sub.1 represents H or halogen; X.sub.1 represents H, halogen, nitro, cyano, formyl, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, C.sub.2-4 alkoxyalkyl, C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkylthio, C.sub.1-6 alkylsulfinyl, C.sub.1-6 alkylsulfonyl, C.sub.2-4 alkenyloxy, C.sub.2-4 alkynyloxy, C.sub.2-4 alkenylthio, C.sub.2-4 alkynylthio, C.sub.1-6 haloalkyl, C.sub.2-6 halo-alkenyl, C.sub.2-6 haloalkynyl, C.sub.1-6 haloalkoxy, C.sub.2-4 haloalkoxyalkyl, C.sub.2-6 haloalkylcarbonyl, C.sub.1-6 haloalkylthio, C.sub.1-6 haloalkylsulfinyl, C.sub.1-6 halo-alkylsulfonyl, C.sub.3-6 trialkylsilyl, C.sub.2-4 haloalkenyloxy, C.sub.2-4 haloalkynyloxy, C.sub.2-4 haloalkenylthio, C.sub.2-4 haloalkynylthio, --C(O)OR.sup.7', --C(O)NR.sup.6'R.sup.7', --CR.sup.6'NOR.sup.7', --NR.sup.6'R.sup.7', --NR.sup.6'OR.sup.7', --NR.sup.6'SO2R.sup.7', --NR.sup.6'C(O)R.sup.7', --NR.sup.6'C(O)OR.sup.7', --NR.sup.6'C(O)NR.sup.6'R.sup.7' or --NCR.sup.6'NR.sup.6'R.sup.7'; R.sup.6' represents H, C.sub.1-4 alkyl or C.sub.1-4 haloalkyl; R.sup.7' represents C.sub.1-4 alkyl or C.sub.1-4 haloalkyl; Y.sub.1 represents H, halogen, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, C.sub.1-6 alkoxy, C.sub.1-6 haloalkoxy, C.sub.2-6 alkenyl or C.sub.2-6 haloalkenyl, or, X.sub.1 and Y.sub.1 taken together, represents --O(CH.sub.2).sub.nnCH.sub.2--, or --O(CH.sub.2).sub.nnO-- wherein nn=1 or 2; and Z.sub.1 represents H or halogen, then Z is other than CO.sub.2H, CO.sub.2Me, CO.sub.2Et, CO.sub.2.sup.nBu or CO.sub.2.sup.-NHEt.sub.3.sup.+.

2. The compound according to claim 1, wherein A is halogen, C.sub.1-4 alkylthio, phenyl optionally substituted by 1-3 groups R.sup.1, or C.sub.3-6 cycloalkyl optionally substituted by 1-4 groups R.sup.2; R.sup.1 is halogen, cyano, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, C.sub.1-4 alkylthio, C.sub.1-4 haloalkylthio, amino, C.sub.1-4 alkylamino, di(C.sub.1-4)alkylamino or two adjacent groups R.sup.1 together with the atoms to which they are joined form a 6-membered aromatic ring, said ring being optionally substituted by 1-2 groups selected from: halogen, cyano, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, C.sub.1-4 alkylthio, C.sub.1-4 haloalkylthio; R.sup.2 is halogen, cyano, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.3-6 cycloalkyl, C.sub.1-4 alkoxy, C.sub.1-4haloalkoxy, C.sub.1-4 alkoxycarbonyl, or C.sub.1-4 alkylaminocarbonyl; or any two geminal R.sup.2 groups together form a group selected from oxo, .dbd.CR.sup.mmR.sup.nn, or .dbd.NOR.sup.oo; or two groups R.sup.2 together with the atoms to which they are joined form a 3-6-membered ring system, said ring system being optionally substituted by 1-2 groups selected from: halogen, cyano, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.1-4 alkoxy, or C.sub.1-4 haloalkoxy; R.sup.mm and R.sup.nn are each independently hydrogen, halogen, cyano, nitro, C.sub.1-4 alkyl, or C.sub.1-4 alkoxycarbonyl; R.sup.oo is hydrogen, C.sub.1-4 alkyl, C.sub.3-6cycloalkyl (C.sub.1-2)alkyl or C.sub.3-6cycloalkyl; X is azido, halogen, C.sub.1-3 alkoxy, C.sub.1-4 alkoxycarbonylC.sub.1-3alkoxy, C.sub.1-4 alkylthio, C.sub.1-4 alkylsulphinyl, C.sub.1-4 alkylsulphonyl or NR.sup.5R.sup.6 wherein R.sup.5 is hydrogen, C.sub.1-4 alkyl optionally substituted with 1 or 2 C.sub.1-4 alkoxy groups, C.sub.1-4 haloalkyl optionally substituted with 1 or 2 C.sub.1-4 alkoxy groups, C.sub.2-4 alkenyl, SO.sub.2R.sup.ss, or C(O)R.sup.uu; R.sup.6 is hydrogen, C.sub.1-4 alkyl optionally substituted with 1 or 2 C.sub.1-4 alkoxy groups, or C.sub.1-4 haloalkyl optionally substituted with 1 or 2 C.sub.1-4 alkoxy groups, C.sub.2-4 alkenyl; R.sup.ss and R.sup.uu are C.sub.1-3 alkyl, Y is C.sub.1-6 alkyl optionally substituted by 1-3 groups R.sup.ba, C.sub.1-6haloalkyl optionally substituted by 1-3 groups R.sup.ba, C.sub.3-6cycloalkyl optionally substituted by 1-3 groups R.sup.bc, C.sub.2-6alkenyl optionally substituted by 1-3 groups R.sup.bd, C.sub.2-6 alkynyl optionally substituted by 1-3 groups R.sup.be, wherein each R.sup.ba is independently cyano, nitro, hydroxyl, C.sub.3-6cycloalkyl, C.sub.1-4 alkoxy, C.sub.1-4alkylthio, C.sub.1-4alkylcarbonyl or C.sub.1-4alkoxycarbonyl, or two geminal R.sup.ba together form an oxo or oximino group; R.sup.bc is halogen, cyano, C.sub.1-4alkyl, C.sub.1-4alkoxy, or C.sub.1-4alkoxycarbonyl; R.sup.bd is halogen, cyano, C.sub.3-6cycloalkyl, C.sub.1-4alkylcarbonyl, or C.sub.1-4 alkoxycarbonyl; R.sup.be is halogen, cyano, hydroxyl, C.sub.1-4alkoxycarbonyl, or C.sub.3-12 trialkylsilyl; and, Z is O.sub.m--(CH.sub.2).sub.n--C(O)R.sup.cb, wherein n is an integer of 0 or 1, m is an integer of 0 or 1, and n=m R.sup.cb is hydroxyl, C.sub.1-10 alkoxy, phenyl C.sub.1-2 alkoxy or NH.sub.2.

3. The compound according to claim 1 or claim 2, wherein A is Cl, phenyl optionally substituted by 1-3 groups R.sup.1, cyclopropyl optionally substituted by 1-2 groups R.sup.2; each R.sup.1 is independently halogen, cyano, C.sub.1-2 alkyl, C.sub.1-2 haloalkyl, C.sub.1-2 alkoxy, C.sub.1-2 haloalkoxy, amino, C.sub.1-4 alkylamino, or di(C.sub.1-4)alkylamino; each R.sup.2 is independently halogen, cyano, C.sub.1-2alkyl, C.sub.1-2 haloalkyl, C.sub.1-2 alkoxy, C.sub.1-2 haloalkoxy or C.sub.2-4 alkoxycarbonyl; X is N.sub.3, Cl, OCH.sub.3, OCH.sub.2CO.sub.2CH.sub.3, NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, NH-i-propyl, SMe, SOMe, SO.sub.2Me, NHCOCH.sub.3, NHC(O)OCH.sub.3, NHSO.sub.2CH.sub.3, NCH.sub.3COCH.sub.3, NCH.sub.3C(O)OCH.sub.3, or NCH.sub.3SO.sub.2CH.sub.3; Y is C.sub.1-3 alkyl, C.sub.1-3 haloalkyl, C.sub.2-5alkoxyalkyl, cyclopropyl optionally substituted by 1 or 2 groups R.sup.bc, C.sub.2-4 alkenyl, C.sub.2-4 haloalkenyl, or C.sub.2-4 alkynyl optionally substituted by 1 or 2 groups R.sup.be, wherein each R.sup.bc is independently halogen or C.sub.1-2 alkyl, and each R.sup.be is independently halogen or C.sub.3-9 trialkylsilyl; and Z is selected from the group consisting of CO.sub.2H, CO.sub.2CH.sub.3, CO.sub.2CH.sub.2CH.sub.3, CO.sub.2-i-propyl, CO.sub.2-n-propyl, CO.sub.2CH.sub.2-i-propyl, CO.sub.2CH.sub.2-Phenyl, CONH.sub.2, OCH.sub.2CO.sub.2H, OCH.sub.2CO.sub.2CH.sub.3.

4. The compound according to any one of the preceding claims wherein A is selected from the group consisting of: Cl, methylthio, isopropyl, cyclopropyl, 2-methylcyclopropyl, 4-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-fluorophenyl, 4-trifluoromethylphenyl, 4-trifluoromethoxyphenyl, 2,4-dimethoxyphenyl, 2,4-dichlorophenyl, 2-chloro-4-methylphenyl, 2-chloro-4-trifluoromethylphenyl, 2-fluoro-4-methylphenyl, 2-fluoro-3-methoxyphenyl, 2-fluoro-4-methoxyphenyl, 2,4-bis(trifluoromethyl)phenyl, 3,4-dimethylphenyl, 3,4-dimethoxyphenyl, 3-chloro-4-methylphenyl, 3-chloro-4-methoxyphenyl, 3,4-dichlorophenyl, 3-chloro-4-fluorophenyl, 3-chloro-4-trifluoromethylphenyl, 3-fluoro-4-methylphenyl, 3-fluoro-4-methoxyphenyl, 4-methyl-3-nitrophenyl, 4-methoxy-2-methylphenyl, 4-chloro-2-methylphenyl, 4-chloro-3-methylphenyl, 4-chloro-2-methoxyphenyl, 4-chloro-3-methoxyphenyl, 4-chloro-3-nitrophenyl, 4-chloro-3-cyanophenyl, 4-chloro-2-fluorophenyl, 4-chloro-3-fluorophenyl, 4-chloro-2-trifluoromethylphenyl, 4-chloro-3-trifluoromethylphenyl, 4-fluoro-3-methylphenyl, 4-fluoro-3-methoxyphenyl, 4-fluoro-3-trifluoromethylphenyl, 2,4,5-trimethylphenyl, 2,3,4-trimethoxyphenyl, 2,3,4-trichlorophenyl, 2,4,5-trichlorophenyl, 2,4,6-trichlorophenyl, 2,3,4-trifluorophenyl, 2,4-dichloro-3-fluorophenyl, 3,4-dichloro-2-fluorophenyl, 4-chloro-2,3-difluorophenyl, 4-chloro-2,6-difluorophenyl, 4-chloro-3,5-difluorophenyl, 2,4-dichloro-6-fluorophenyl, 4-chloro-2-fluoro-3-methoxyphenyl, 4-chloro-2-fluoro-3-trifluoromethylphenyl, 4-chloro-3-dimethylamino-2-fluorophenyl, and 2-fluoro-3-methoxy-4-methylphenyl; Y is selected from the group consisting of: methyl, ethyl, isopropyl, n-propyl, prop-1-en-2-yl, prop-1-enyl, prop-2-enyl, but-1-enyl, pent-1-enyl, difluoromethyl, trifluoromethyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1-methylprop-1-enyl, 2-methylprop-1-enyl, 1,2-dimethylprop-1-enyl, 3-methylbut-1-ynyl, 3-methylbut-2-enyl, 3,3-dimethylbut-1-ynyl, acetyl, formyl, methoxymethyl, 2-methoxyethyl, hydroxyiminomethyl, methoxyiminomethyl, 1-(hydroxyimino)ethyl, 1-(methoxyimino)ethyl, cyclopropyl, 1-methylcyclopropyl, 2,2-dichlorocyclopropyl, vinyl, 2-cyclopropylvinyl, 1-ethoxyvinyl, 2,2-dichlorovinyl, ethynyl, prop-1-ynyl, 2-bromoethynyl, 2-chloroethynyl, and 2-trimethylsilylethynyl.

5. A compound according to any one of claim 1, 2 or 4 wherein A is optionally substituted alkylthio.

6. A compound according to any preceding claim wherein X is azido, halogen, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkylsulphinyl or optionally substituted alkylsulphonyl.

7. A compound according to any preceding claim wherein n is 1.

8. A herbicidal composition comprising a compound as defined in any one of the preceding claims and at least one agriculturally acceptable formulation adjuvant or diluent.

9. The herbicidal composition according to claim 8, further comprising a crop safener.

10. A compound as defined in any one of claims 1 to 7, or a herbicidal composition according to claim 8 or claim 9, in admixture with at least one active ingredient selected from the group consisting of: an insecticide, an acaricide, a nematocide, a molluscicide, an herbicide, a fungicide, and a plant growth regulator.

11. Use of a compound according to any one of claims 1 to 7 as a herbicide.

12. A method of controlling weeds in crops of useful plants which comprises applying to said weeds or to the locus of said weeds, or to said crop of useful plants, a compound as defined in any one of claims 1 to 7, or a herbicidal composition according to claim 8 or claim 9, or a mixture according to claim 10.

13. A compound of formula (II) ##STR00229## wherein R.sup.7 is methyl, Br, or Cl; R.sup.8 is H, F, Cl, OR.sup.10, or N(R.sup.10).sub.2; R.sup.9 is H, F, or Cl; and each R.sup.10 is independently H or C.sub.1-4alkyl, provided that (i) R.sup.8 and R.sup.9 are not both hydrogen, (ii) when R.sup.7 is methyl and R.sup.9 is hydrogen, then R.sup.8 is not F, Cl, or NH.sub.2, (iii) when R.sup.7 is Cl and R.sup.8 is hydrogen, R.sup.9 is not Cl, (iv) when R.sup.7 is Cl and R.sup.8 is Cl, R.sup.9 is not hydrogen, and (v) when R.sup.7 is Br and R.sup.9 is hydrogen, R.sup.8 is not F.

14. A process for the preparation of a compound of formula (T) ##STR00230## or salt or N-oxide thereof, wherein: A is halogen, optionally substituted alkylthio, optionally substituted alkyl, optionally substituted alkenyl or an optionally substituted 3-8 membered carbocyclic ring; Y' is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, or optionally substituted alkynyl; and, Z' is hydroxyl or CHR.sup.w).sub.n--C(O)R.sup.cb, wherein n is an integer of 0 or 1 R.sup.w is hydrogen or C.sub.1-4 alkyl R.sup.cb is hydroxy, optionally substituted alkylthio, NH.sub.2, or OR.sup.co, R.sup.co is C.sub.1-20 alkyl optionally substituted by 1-3 groups R.sup.cq, or C.sub.1-20 haloalkyl optionally substituted by 1-3 groups R.sup.cq; each R.sup.cq is independently C.sub.1-6 alkoxy, phenyl optionally substituted by 1-3 groups R.sup.cr, or heteroaryl optionally substituted by 1-2 groups R.sup.cs; each R.sup.cr and each R.sup.cs are independently halogen, cyano, C.sub.1-4 alkyl, C.sub.1-4 haloalkyl, C.sub.2-6 alkoxyalkyl, C.sub.1-4 alkoxy, C.sub.1-4 haloalkoxy, C.sub.1-4 alkylsulphonyl, or C.sub.1-4 alkoxycarbonyl comprising reacting an amidine of formula (N) ##STR00231## wherein A is as defined above, or a salt form thereof, with a keto ester of the formula (U) ##STR00232## or a salt form thereof, wherein Y' and Z' are as defined above, or Z' is OR, and R is selected from hydrogen or alkyl.

15. A process according to claim 14 comprising the further step or steps of converting the compound of formula (T) to a compound of formula (I) ##STR00233## wherein A, Z and Y are as defined in claim 14, and X is azido, halogen, optionally substituted alkoxy, optionally substituted alkylthio, optionally substituted alkylsulphyl, optionally substituted alkylsulphonyl or NR.sup.5R.sup.6; R.sup.5 is hydrogen, C.sub.2-4 alkenyl, SO.sub.2R.sup.ss, C(O)R.sup.uu or optionally substituted C.sub.1-4 alkyl; R.sup.6 is hydrogen, C.sub.2-4 alkenyl or optionally substituted C.sub.1-4 alkyl; each R.sup.ss is independently C.sub.1-4 alkyl or phenyl optionally substituted by 1-3 groups R.sup.zz; each R.sup.uu is independently C.sub.1-4 alkyl, phenyl optionally substituted by 1-3 groups R.sup.zz, C.sub.1-4 alkoxy, or NR.sup.acR.sup.ad; each R.sup.zz is independently halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, or C.sub.1-4 alkylsulphonyl; R.sup.ac and R.sup.ad are each independently hydrogen or C.sub.1-4 alkyl; or R.sup.5 and R.sup.6 together form a group .dbd.C(R.sup.i)OR.sup.j, .dbd.C(R.sup.k)SR.sup.l, .dbd.C(R.sup.m)NR.sup.nR.sup.o wherein R.sup.i is hydrogen, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, phenyl, C.sub.1-4 alkoxy, C.sub.1-4 alkylthio, or NR.sup.acR.sup.ad wherein R.sup.ac and R.sup.ad are as defined above, R.sup.j and R.sup.l are each independently C.sub.1-4 alkyl, R.sup.k is hydrogen, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, phenyl, C.sub.1-4 alkylthio, or NR.sup.acR.sup.ad wherein R.sup.ac and R.sup.ad are as defined above, R.sup.m is hydrogen, C.sub.1-4 alkyl, C.sub.3-6 cycloalkyl, phenyl, or NR.sup.acR.sup.ad wherein R.sup.ac and R.sup.ad are as defined above, and R.sup.n and R.sup.o are each independently hydrogen or C.sub.1-4 alkyl, or a salt form thereof.